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1
Spence, Michael Patrick. "Plant aromatic amino acid decarboxylases: Evolutionary divergence, physiological function, structure function relationships and biochemical properties." Diss., Virginia Tech, 2014. http://hdl.handle.net/10919/49432.
Повний текст джерелаАнотація:
Plant aromatic amino acid decarboxylases (AAADs) are a group of economically important enzymes categorically joined through their pyridoxal 5'-phosphate (PLP) dependence and sequence homology. Extensive evolutionary divergence of this enzyme family has resulted in a selection of enzymes with stringent aromatic amino acid substrate specificities. Variations in substrate specificities enable individual enzymes to catalyze key reactions in a diverse set of pathways impacting the synthesis of monoterpenoid indole alkaloids (including the pharmacologically active vinblastine and quinine), benzylisoquinoline alkaloids (including the pharmacologically active papaverine, codeine, morphine, and sanguinarine), and antioxidant and chemotherapeutic amides. Recent studies of plant AAAD proteins demonstrated that in addition to the typical decarboxylation enzymes, some annotated plant AAAD proteins are actually aromatic acetaldehyde synthases (AASs). These AASs catalyze a decarboxylation-oxidative deamination process of aromatic amino acids, leading to the production of aromatic acetaldehydes rather than the AAAD derived arylalkylamines. Research has implicated that plant AAS enzymes are involved in the production of volatile flower scents, floral attractants, and defensive phenolic acetaldehyde secondary metabolites. Historically, the structural elements responsible for differentiating plant AAAD substrate specificity and activity have been difficult to identify due to strong AAAD and AAS inter-enzyme homology. Through extensive bioinformatic analysis and experimental verification of plant AAADs, we have determined some structural elements unique to given types of AAADs. This document highlights structural components apparently responsible for the differentiation of activity and substrate specificity. In addition to producing primary sequence identifiers capable of AAAD activity and substrate specificity differentiation, this work has also demonstrated applications of AAAD enzyme engineering and novel activity identification.Ph. D.
2
Allen, G. F. G. "The neurochemical consequences of aromatic L-amino acid decarboxylase deficiency." Thesis, University College London (University of London), 2011. http://discovery.ucl.ac.uk/1310134/.
Повний текст джерелаАнотація:
Aromatic L-amino acid decarboxylase (AADC) catalyses the conversion of 5-hydroxytryptophan (5-HTP) and L-3,4-dihydroxyphenylalanine (L-dopa) to the neurotransmitters serotonin and dopamine respectively. The inherited disorder AADC deficiency leads to a severe deficit of serotonin and dopamine as well as an accumulation of 5-HTP and L-dopa. This thesis investigated the potential role of 5-HTP/L-dopa accumulation in the pathogenesis of AADC deficiency. Treatment of human neuroblastoma cells with L-dopa or dopamine was found to increase intracellular levels of the antioxidant reduced glutathione (GSH). However inhibiting AADC prevented the GSH increase induced by L-dopa. Furthermore dopamine but not L-dopa, increased GSH release from human astrocytoma cells, which do not express AADC activity. GSH release is the first stage of GSH trafficking from astrocytes to neurons. This data indicates dopamine may play a role in controlling brain GSH levels and consequently antioxidant status. The inability of L-dopa to influence GSH concentrations in the absence of AADC or with AADC inhibited indicates GSH trafficking/metabolism may be compromised in AADC deficiency. 5-HTP was demonstrated to potentially be mildly toxic to human neuroblastoma cells but not astrocytoma cells; however the concentrations required for this response are likely to be higher than pathophysiological levels in AADC deficiency. These results indicate the need for investigations addressing the effects of chronic 5-HTP exposure as only acute effects were investigated in the current study. This thesis also investigated the effect of altered availability of the AADC coenzyme pyridoxal 5‟-phosphate (PLP) on AADC activity, protein and expression. In two patients with inherited disorders of PLP metabolism reductions in plasma AADC activity were observed. Furthermore PLP-deficient human neuroblastoma cells were found to exhibit reduced levels of AADC activity and protein but not altered expression. These findings suggest maintaining adequate PLP availability may be important for optimal treatment of AADC deficiency.
3
Fisher, Andrew. "Pharmacological manipulation of aromatic L-amino acid decarboxylase in the rat." Thesis, University College London (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.325114.
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4
Cho, Seongeun. "Modulation of tyrosine hydroxylase and aromatic L-amino acid decarboxylase by dopaminergic drugs in mouse brain /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu148786592945682.
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5
Liang, Jing. "Biochemical Studies of Aromatic Amino Acid Decarboxylases and Acetaldehyde Synthases." Diss., Virginia Tech, 2018. http://hdl.handle.net/10919/96242.
Повний текст джерелаАнотація:
Pyridoxal 5'-phosphate (PLP)-dependent enzymes widely exist in most living organisms from bacteria to human. Among different types of PLP-dependent enzymes, aromatic amino acid decarboxylases play critical physiological roles because many aromatic amines are essential neurotransmitters. This dissertation concerns the biochemical characterization of several PLP-dependent decarboxylases and aims to understand the structure-function relationships, especially critical residues involved in their catalysis. We first present an overview of the current opinions and recent advances in structure-function relationships of several PLP-dependent enzymes with the first reaction step at substrate Cα position, including decarboxylase and acetaldehyde synthase. L-3, 4-dihydroxyphenylalanine (L-dopa) decarboxylase (DDC) is a model enzyme we use as a reference because the structures and functions of DDC are relatively well established. We previously identified two annotated DDC-like proteins from Drosophila indeed catalyzing a decarboxylation-oxidative deamination reaction of L-dopa to form 3,4-dihydroxyphenylacetaldehyde (DHPA), CO2, NH3, and H2O2 and we named these proteins as DHPA synthases due to the physiological importance of DHPA for cuticle protein crosslinking. Our results provide an efficient way to identify more DHPA synthase enzymes from DDC based on sequence identity and the signature residues we identified (Asn192 in DHPA synthase versus His192 in DDC), and we also propose a reasonable explanation of the mechanism. The results that H2O2 produced by the reaction can be reused in the reaction as an oxidizing agent suggest a way to avoid the oxidative stress of H2O2. We then compared tyrosine decarboxylase (TyDC) with DDC. As the enzyme catalyzing the first step of insect neurotransmitter tyramine/octopamine synthesis, the biochemical characteristics of insect TyDC have not been thoroughly elucidated yet because of the expression difficulty. We expressed one insect TyDC and analyzed its biochemical properties. Our enzyme analyses reveal that insect TyDC prefers tyrosine as a substrate, but it also displays some activity to L-dopa. Spectral analysis also shows that the absorbance spectra of insect TyDC have major differences as compared to those of DDC. Site-directed mutagenesis indicates that the interactions between residue Asn304 with PLP is primarily responsible for its spectra differences of TyDC as compared to those of DDC and also is involved in higher substrate affinity to L-tyrosine. Another active site residue (Ser353) has the main effect on substrate selectivity. Our results show the biochemical properties of TyDC for the first time and also provide some insights into the mechanism of its substrate selectivity.PHD
6
Phillips, Susan R. "Spectroscopic investigation of tryptophan microenvironments in bovine lens proteins." Diss., Georgia Institute of Technology, 1986. http://hdl.handle.net/1853/32973.
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7
Silvia, Christopher Paul. "The isolation, partial peptide sequence, and cDNA sequence of aromatic L-amino acid decarboxylase from bovine adrenal medulla /." The Ohio State University, 1990. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487677267729241.
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8
Young, Elizabeth A. "Second Messenger System Modulation of Aromatic L-Amino Acid Decarboxylase and Tyrosine Hydroxylase in Normal and MPTP Lesioned Mice /." The Ohio State University, 1995. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487929230741091.
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9
Höfig, Carolin. "Establishment, validation and application of immunological and LC-MS/MS-based detection methods to study the role of human aromatic L-amino acid decarboxylase as an enzyme potentially involved in thyronamine biosynthesis." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://dx.doi.org/10.18452/16645.
Повний текст джерелаАнотація:
Thyronamine (TAM) sind eine neue Molekülklasse, die endokrinologische und metabolische Prozesse miteinander vereinen. Der biologisch aktive Metabolit 3-Iod-L-Thyronamin (3-T1AM) wird durch eine kombinierte Deiodierung und Decarboxylierung von Schilddrüsenhormonen (TH) gebildet. Existierende Methoden zum Nachweis und zur Quantifizierung von 3-T1AM im menschlichen Serum sind immer noch umstritten. Auch die an der Biosynthese vermutlich beteiligte TH-Decarboxylase konnte noch nicht identifiziert werden. Für die Identifizierung und Quantifizierung von TH und TAM Profilen wurde die Flüssigchromatographie-Tandem-Massenspektrometrie (LC-MS/MS) verwendet. In der bisherigen präanalytischen Aufarbeitung liefern weder Flüssig-Flüssig- noch Festphasenextraktionen reproduzierbare Ergebnisse des 3-T1AM-Gehalts im Serum. Mit der Entwicklung eines spezifischen Extraktionsverfahrens und nachfolgender Detektion mittels LC-MS/MS gelang der gleichzeitige Nachweis der häufigsten TH im humanen Serum. Parallel dazu wurden monoklonale Antikörper gegen 3-T1AM entwickelt, auf deren Basis ein quantitativer 3-T1AM Chemilumineszenz-Immunoassay entstand. Ergebnisse aus klinischen Kollektiven zeigen, dass 3-T1AM im Serum im nM Konzentrationsbereich vorkommt und dass 3-T1AM bei Patienten außerhalb der Schilddrüse produziert wird. Viele Forscher gehen davon aus, dass die aromatische L-Aminosäure Decarboxylase (AADC) die Synthese von TAM über Decarboxylierung von TH katalysiert. Diese Hypothese wurde durch Inkubation von rekombinanter humaner AADC mit TH getestet. In keinem der Experimente konnte AADC die Decarboxylierung von TH katalysieren. Zusammenfassend ist die Bestimmung von 3-T1AM im Serum mittels LC-MS/MS aufgrund der nicht reproduzierbaren präanalytischen Probenaufbereitung problematisch. In dieser Arbeit wird der erste MAb-basierte 3-T1AM assay vorgestellt, der 3-T1AM zuverlässig in humanem Serum quantifiziert. Die AADC ist wahrscheinlich nicht an der Biosynthese von TAM beteiligt.Thyronamines (TAM) are a new class of molecules linking endocrinology and metabolism. Combined deiodination and decarboxylation of thyroid hormones (TH) generates a biologically active ‘cooling’ metabolite, 3-iodo-L-thyronamine (3-T1AM).. It remains controversial, which methods are able or not to reliably detect 3-T1AM in human serum, and the presumed TH decarboxylase is still elusive. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for the simultane-ous identification and quantification of TH and TAM profiles in biological samples. Several preanalytical methods were tested for complete extraction of 3-T1AM in human serum. Thus far, neither liquid-liquid nor solid-phase extraction methods allowed reproducible extraction of 3-T1AM from human serum samples in the preanalytical sample workup. Nevertheless, a rapid and sensitive extraction procedure was developed for detection of the major TH by LC-MS/MS in a single human serum sample. In parallel, monoclonal antibodies (MAb) targeting 3-T1AM were developed and characterized, and a highly specific quantitative 3-T1AM MAb-based chemiluminescence immunoassay was developed. Studies in clinical cohorts provide evidence that 3-T1AM is present in human serum in the nM concentration range and that 3-T1AM is produced extrathyroidally. Many researchers have reasoned that the aromatic L-amino acid decarboxylase (AADC) mediates TAM synthesis via decarboxylation of TH. This hypothesis was tested by incubating recombinant human AADC with several TH. In all tested conditions, AADC failed to catalyze the decarboxylation of TH. These in vitro observations are supported by the finding that 3-T1AM is also present in plasma samples of patients with AADC deficiency. In summary, 3-T1AM detection in serum using LC-MS/MS encounters preanalytical problems. The first MAb-based 3-T1AM CLIA is presented, which reliably quantifies 3-T1AM in human serum. AADC is likely not involved in TAM biosynthesis.
10
Höfig, Carolin [Verfasser], Werner [Akademischer Betreuer] Kloas, Josef [Akademischer Betreuer] Köhrle, and Dagmar [Akademischer Betreuer] Führer-Sakel. "Establishment, validation and application of immunological and LC-MS/MS-based detection methods to study the role of human aromatic L-amino acid decarboxylase as an enzyme potentially involved in thyronamine biosynthesis / Carolin Höfig. Gutachter: Werner Kloas ; Josef Köhrle ; Dagmar Führer-Sakel." Berlin : Humboldt Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, 2012. http://d-nb.info/1029763844/34.
Повний текст джерела
11
Gebre-Medhin, Gennet. "Clinical and experimental studies of organ-specific autoimmune diseases : With special reference to Addison's disease and autoimmune hepatitis : by Gennet Gebre-Medhin." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Univ.-bibl. [distributör], 2001. http://publications.uu.se/theses/91-554-5043-1/.
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12
Chu, Yi-wen 1962. "Amino acid sequence requirements for ornithine decarboxylase activity." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276838.
Повний текст джерелаАнотація:
ODC activity of the altered proteins was measured and compared to that of the full length 461 amino acid containing ODC. Mouse ODC cDNA sequences were deleted from either 5' or 3' ends using exonuclease III and Mung Bean nuclease treatments. An internal deletion was obtained by Hinc II and Bcl I restriction endonuclease digestion of the full length ODC cDNA. Capped mRNAs were synthesized in vitro using the resulting deleted DNA as templates, and the protein was translated in vitro. The results indicate that the protein in which translation initiates at internal AUG start codons does not have any activity. The protein with 39 amino acids deleted from carboxy-terminus maintains 12% of the activity, while deletion of greater than 79 amino acids have no activity. An internal deletion from amino acid 290 to 331 and which may contain the suspected ornithine binding site has no activity. These results suggest that the entire amino acid sequence of mouse ODC is required for full activity of the enzyme.
13
Pigeon, Dominique. "Etude des enzymes de synthèse des catécholamines et phosphorylation de la tyrosine hydroxylase de phéochromocytome de rat." Paris 6, 1986. http://www.theses.fr/1986PA066168.
Повний текст джерелаАнотація:
La structure et le régulation des enzymes de synthèse des catécholamines ont été étudiées dans le phéochromocytome de rat. Nous avons mis au point un protocole permettant la séparation des trois premiers enzymes de la voie de synthèse. Ceci a permis de purifier partiellement la dopamine beta -hydroxylase et de mettre en évidence son inhibiteur endogène, qui a été décrit pour la première fois. Nous avons montré qu'une activité protéine kinase était copurifiée avec la tyrosine hydroxylase, qu'elle phosphoryle. Cette activité a été caractérisé et la séquence primaire du site de phosphorylation a été déterminée.
14
Banerji, Suneale. "Aromatic amino acid biosynthesis in Pneumocystis carinii." Thesis, University of Oxford, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336091.
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15
Salter, M. "Aromatic amino acid metabolism in the rat liver." Thesis, University of Manchester, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.374780.
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16
Brown, Judy Forsyth. "Regulation in aromatic amino acid biosynthesis in Saccharomyces cerevisiae." Thesis, University of Edinburgh, 1987. http://hdl.handle.net/1842/12947.
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17
Ikeda, Masato. "Molecular Breeding of Aromatic Amino Acid-Producing Corynebacterium glutamicum." Kyoto University, 1995. http://hdl.handle.net/2433/160852.
Повний текст джерелаАнотація:
本文データは平成22年度国立国会図書館の学位論文(博士)のデジタル化実施により作成された画像ファイルを基にpdf変換したものであるKyoto University (京都大学)
0048
新制・論文博士
博士(農学)
乙第8803号
論農博第1966号
新制||農||695(附属図書館)
学位論文||H7||N2779(農学部図書室)
UT51-95-B268
(主査)教授 駒野 徹, 教授 大山 莞爾, 教授 加藤 暢夫
学位規則第4条第2項該当
18
Niemand, Jandeli. "A phage display study of interacting peptide binding partners of malarial S-Adenosylmethionine decarboxylase/Ornithine decarboxylase." Diss., University of Pretoria, 2007. http://hdl.handle.net/2263/24105.
Повний текст джерелаАнотація:
Due to the increasing resistance against the currently used antimalarial drugs, novel chemotherapeutic agents that target new metabolic pathways for the treatment of malarial infections are urgently needed. One approach to the drug discovery process is to use interaction analysis to find proteins that are involved in a specific metabolic pathway that has been identified as a drug target. Protein-protein interactions in such a pathway can be preferential targets since a) there is often greater structural variability in protein-protein interfaces, which can lead to more effective differentiation between the parasite and host proteins; and b) the important amino acids in a protein-protein interface are often conserved and even one amino acid mutation can lead to the dissociation of the complex, implying that resistance should be slower to appear. Since polyamines and their biosynthetic enzymes occur in increased concentrations in rapidly proliferating cells, the inhibition of polyamine metabolism is a rational approach for the development of antiparasitic drugs. Polyamine synthesis in P. falciparum is uniquely facilitated by a single open reading frame that encodes both rate-limiting enzymes in the pathway, namely ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase (AdoMetDC). The AdoMetDC/ODC domains are assembled in a heterotetrameric bifunctional protein complex of ~330 kDa. Inhibition of both decarboxylase activities is curative of murine malaria and indicates the viability of such strategies in malaria control. It was hypothesized that protein ligands to this enzyme can be utilized in targeting the polyamine biosynthetic pathway in a novel approach. The bifunctional PfAdoMetDC/ODC was recombinantly expressed with a C-terminal Strep-tag-II to allow affinity purification. Subsequent gel electrophoresis analysis showed the presence of 3 contaminating proteins (~60 kDa, ~70 kDa and ~112 kDa) that co-elute with the ~330 kDa AdoMetDC/ODC. Efforts to purify the bifunctional protein to homogeneity included subcloning into a double-tagged vector for tandem affinity purification as well as size-exclusion HPLC. SDS-PAGE analysis of these indicated that separation of the four proteins was not successful, implicating the presence of strong protein-protein interactions. Western blot analysis showed that the ~112 kDa and ~70 kDa peptides were recombinantly produced with a C-terminal Strep-tag, indicating their heterologous origin. The ~60 kDa fragment was however not recognised by the tag-specific antibodies. This implies that this fragment is of E. coli origin. MS-analysis of the contaminating bands showed that the ~112 kDa peptide is an N-terminally truncated form of the full-length protein, the ~70 kDa peptide is a mixture of N-terminally truncated recombinant protein and E. coli DnaK and the ~60 kDa peptide is E. coli GroEL. A P. falciparum cDNA phage display library was used to identify peptide ligands to PfAdoMetDC/ODC. Of the peptides isolated through the biopanning process, only one was shown to occur in vivo. It could however not be conclusively shown that the isolated peptides bind to PfAdoMetDC/ODC and not to the co-eluting E. coli proteins. It is thought that while it is extremely likely that interacting protein partners to PfAdoMetDC/DOC exist, the available technologies are not sufficient to lead to the identification of such partners.Dissertation (MSc (Biochemistry))--University of Pretoria, 2008.
Biochemistry
unrestricted
19
Stuart, Fiona. "An investigation of aromatic amino acid biosynthesis in Streptomyces rimosus." Thesis, University of Glasgow, 1990. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.506454.
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20
Butchosa, Robles Cristina. "Computational modeling of charge transfer in nucleobase-aromatic amino acid complexes." Doctoral thesis, Universitat de Girona, 2012. http://hdl.handle.net/10803/83529.
Повний текст джерелаАнотація:
The present thesis models nucleobase-amino acid charge transfer reactions, which can serve as base for future computational investigations of charge transfer processes in DNA-protein systems. Guanine and adenine charge transfer reactions with aromatic amino acids (histidine, phenylalanine, tryptophan, and tyrosine) have been studied. Both pi-stacked and T-shaped nucleobase-aromatic amino acid interactions have been found to produce fast charge transfer rates. Most of the aromatic amino acids are able to extract charges from DNA. Special attention has been paid to tryptophan because its redox properties. Tryptophan is the best aromatic amino acid to extract cationic charges from guanine and adenine.The studied interactions have been shown to be extremely sensitive to conformational fluctuations.Aquesta tesis doctoral modelitza reaccions de transferència de càrrega en sistemes compostos per una nucleobase i un aminoàcid. Un millor coneixement d’aquestes interaccions pot servir com a base per futures investigacions de processos de transferència de càrrega en sistemes ADN-proteïna. S’han estudiat les reaccions de transferència de càrrega de la guanina o adenina amb aminoàcids aromàtics (histidina, fenilalanina, triptòfan i tirosina). Especialment, les interaccions amb el triptòfan, que gràcies a un potencial de ionització semblant al de la guanina pot estabilitzar millor que els altres aminoàcids un estat radical catió. S’han considerat tant interaccions dels sistemes pi com conformacions en forma T del les parelles nucleobase-aminoàcid, obtenint velocitats de reacció ràpides. La majoria d’aminoàcids aromàtics són capaços d’extreure càrregues de l’ADN. Les interaccions estudiades s’han mostrat molt sensibles a fluctuacions conformacionals.
21
Gulko, Miriam Kolog. "A non-canonical pathway for aromatic amino acid biosynthesis in haloarchea." Diss., lmu, 2010. http://nbn-resolving.de/urn:nbn:de:bvb:19-131276.
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22
Gartland, Martin John. "Site-directed mutagenesis of the aromatic amino acid aminotransferase of Escherichia coli." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.293014.
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23
Alexander, Janet Elizabeth. "Construction and characterisation of aromatic amino acid dependent mutants of Listeria monocytogenes." Thesis, University of Leicester, 1993. http://hdl.handle.net/2381/35379.
Повний текст джерелаАнотація:
The severe forms of listeriosis, have a very high mortality rate. In farm animals, especially sheep, these losses can be of considerable economic importance. The increase in cases of listeriosis in both man and animals over the last decade has stimulated research to develop an effective vaccine to protect against Listeria monocytogenes. However, attempts at protection using killed or chemically attenuated live vaccines have been disappointing. An alternative to these procedures is the development of strains with a defined mechanism of attenuation. Attempts were made to construct aromatic amino acid dependent mutant strains of L. monocytogenes and to investigate their efficacy as a vaccine. Two strategies were used for the transposon mutagenesis of L. monocytogenes. Suicide vectors carrying transposon Tn917 and unable to replicate in Listeria were constructed. To facilitate the transformation of these vectors into Listeria species an efficient electrotransformation system was developed. However, this procedure was unsuccessful in generating Tn917 insertion mutants. Insertional mutagenesis of L. monocytogenes EGD with Tn917 was achieved using a temperature sensitive plasmid. An aromatic amino acid requiring mutant deficient in chorismate mutase activity was isolated. The multiplication of this mutant was found to be unimpaired in both mouse tissues and cultured bone marrow derived macrophages. Organisms isolated from infected tissues were found to be prototrophic while still harbouring a Tn917 insertion. It was concluded that the original mutant carried a point mutation in the gene encoding chorismate mutase and that this had reverted on passage through the mouse. A transposon induced aromatic amino acid dependent mutant of L. monocytogenes found to be deficient in prephenate dehydratase activity was obtained for investigation. The virulence and multiplication of this mutant were reduced in the mouse. Vaccination with this mutant was found to stimulate a protective immune response in mice. The results indicate that aromatic amino acid dependent mutants of L monocytogenes protect against listeric infection and offer a new approach to the development of anti-listerial vaccines.
24
De, Villiers Jandre. "Synthesis and evaluation of halogenated amino acid analogues as inhibitors of decarboxylase enzymes of selected pathogens." Thesis, Stellenbosch : University of Stellenbosch, 2010. http://hdl.handle.net/10019.1/4498.
Повний текст джерелаАнотація:
Thesis (PhD (Chemistry and Polymer Science))--University of Stellenbosch, 2010.ENGLISH ABSTRACT: The use of fluorine in medicinal chemistry has increased dramatically in the last 20 years. The addition of fluorine to a lead compound has various advantages such as the blocking of metabolic active sites, the increase of solubility and lipophilicity of a compound, acting as conformational probes for the active site of an enzyme, and influencing (in most cases increasing) the binding affinity of a compound to a target protein. Their use as mechanism based inhibitors is also well known. In this study we set out to synthesize hydroxyl- and fluorinated-amino acid analogues as potential inhibitors and probes towards the active site of various enzymes. The synthesis of the hydroxylamino acid analogues would precede the fluorinated analogues to serve as precursors with fuorination achieved via a fluoro-dehydroxylation reaction. These aims have successfully been achieved with the synthesis of the two enantiopure isomers of 3-fluoro-aspartic acid. The fluorinated aspartic acid analogues were subsequently used in a conformational analysis, with regards to substrate- and binding activity, which investigated the interaction of these compounds with aspartate decarboxylase (PanD). The synthesis of the 3- hydroxy-analogues of ornithine and diamino pimelic acid was also successfully achieved. These syntheses were done in a stereospecific manner to provide one enantiomer of the L-amino acid analogue. However, our efforts toward the synthesis of the other enantiomer of hydroxy analogues as well as our attempts at the conversion of the hydroxyl group to a fluorine were unsuccessful to date. Nevertheless, these results gave us a new direction towards the synthesis of the desired compounds and have led us to new strategies and ideas. Hopefully, the work done in this study will be part of the ground work towards new methodologies for the synthesis of desired halogenated amino acid analogues as small molecule inhibitors.
AFRIKAANSE OPSOMMING: The use of fluorine in medicinal chemistry has increased dramatically in the last 20 years. The addition of fluorine to a lead compound has various advantages such as the blocking of metabolic active sites, the increase of solubility and lipophilicity of a compound, acting as conformational probes for the active site of an enzyme, and influencing (in most cases increasing) the binding affinity of a compound to a target protein. Their use as mechanism based inhibitors is also well known. In this study we set out to synthesize hydroxyl- and fluorinated-amino acid analogues as potential inhibitors and probes towards the active site of various enzymes. The synthesis of the hydroxylamino acid analogues would precede the fluorinated analogues to serve as precursors with fuorination achieved via a fluoro-dehydroxylation reaction. These aims have successfully been achieved with the synthesis of the two enantiopure isomers of 3-fluoro-aspartic acid. The fluorinated aspartic acid analogues were subsequently used in a conformational analysis, with regards to substrate- and binding activity, which investigated the interaction of these compounds with aspartate decarboxylase (PanD). The synthesis of the 3- hydroxy-analogues of ornithine and diamino pimelic acid was also successfully achieved. These syntheses were done in a stereospecific manner to provide one enantiomer of the L-amino acid analogue. However, our efforts toward the synthesis of the other enantiomer of hydroxy analogues as well as our attempts at the conversion of the hydroxyl group to a fluorine were unsuccessful to date. Nevertheless, these results gave us a new direction towards the synthesis of the desired compounds and have led us to new strategies and ideas. Hopefully, the work done in this study will be part of the ground work towards new methodologies for the synthesis of desired halogenated amino acid analogues as small molecule inhibitors.
25
Gaskell, Elizabeth Anne. "Metabolic reconstruction and validation: characterisation of two aromatic amino acid hydroxylases from Toxoplasma gondii." Thesis, University of Leeds, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.493552.
Повний текст джерелаАнотація:
The Apicomplexa are a phylum of single celled parasitic organisms that cause a wide range of diseases from human malaria and encephalitis in AlDs patients to coccidiosis in chickens and East Coast fever in cattle. There has been a huge effort in recent years to sequence the genomes of many of these pathogens. This thesis begins by taking a comparative genomics approach to predict novel metabolic pathways from the newly sequenced genomes of Toxoplasma gondii and Eimeha tenella.
26
Hepworth, Peter. "Conformational analysis via LIF spectroscopy of jet cooled molecules : hydroxy- and amino-benzoic acid esters." Thesis, University of Nottingham, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.335925.
Повний текст джерела
27
JEBAI, FATME. "Synthese et ingenierie de l'aromatic l-amino acid decarboxylase aadc (e. C. 4. 1. 1. 28) du rat." Paris 7, 1997. http://www.theses.fr/1997PA077119.
Повний текст джерелаАнотація:
La decarboxylase des acides amines aromatiques (aadc), deuxieme enzyme de la voie de biosynthese des cathecholamines (dopamine, adrenaline, noradrenaline) et des indolamines (serotonine, melatonine), utilise le pyridoxal-5'-phosphate (plp) comme coenzyme, elle appartient au groupe ii de la famille alpha des enzymes a plp. Ce memoire, est la description de l'approche genetique de l'etude structurale de l'aadc du pheochromocytome de rat. Il est presente en deux parties : i- etude de plusieurs vecteurs d'expression permettant d'optimiser la production de l'aadc dans le cytoplasme d'e. Coli : le vecteur d'expression pet 20b+ s'est revele particulierement approprie a notre problematique. Il permet la purification de la proteine aadc, supplementee de 6 histidines a l'extremite c terminale. Cette proteine est caracterisee par son activite specifique elevee, elle possede des proprietes pyhsico-chimiques semblables a celles obtenues pour l'aadc extraite de tissus de mammiferes. Ii- la construction par mutagenese dirigee de plusieurs mutants de l'aadc. L'expression dans e. Coli, ainsi que la caracterisation de chaque mutant par ses proprietes enzymatiques : dans cette etude nous avons utilise la methode hca (hydrophobic cluster analysis) pour predire la structure approchee de l'aadc, a partir de celles deja connues de l'aspartate aminotransferase, de la tryptophanase et de la 2,2-dialkylglycine decarboxylase. Cette etude nous a ainsi permis de localiser un certain nombre de residus du site actif de cette proteine. Nous nous sommes interesses, en particulier, a l'etude de trois acides amines (d271, c311, t246) susceptibles de participer au site enzymatique de cette enzyme. Ainsi on a pu montre que le residu d271 joue un role crucial au cours du mecanisme reactionnel de l'aadc, il forme une liaison hydrogene avec l'azote n(1) du plp, que l'acide amine t246 est probablement implique dans la fixation du substrat et que le residu cys 311 joue un role structural important pour l'aadc.
28
Kocabas, Pinar. "Aromatic Synthesis Performance Of Bacillus Acidocaldarius." Master's thesis, METU, 2004. http://etd.lib.metu.edu.tr/upload/2/12605176/index.pdf.
Повний текст джерелаАнотація:
In this study, the effects of bioprocess operation parameters on aromatic amino acid synthesis performance of Bacillus acidocaldarius were investigated. Firstly, in laboratory scale shake-bioreactors, a defined medium was designed in terms of its carbon and nitrogen sources, to achieve the highest cell concentration. Thereafter, the effects of bioprocess operation parameters, i.e., pH and temperature were investigatedand the optimum medium contained (kg m-3): fructose, 8
(NH4)2HPO4, 5
CaCl2, 0.2
KH2PO4, 2
NaH2PO4.2H2O, 7.318
Na2HPO4, 0.0438
Mg(CH3COO)2.4H2O, 87×
10-3
1 , MgSO4.7H2O
2×
10-3, FeSO4.7H2O
2×
10-3, ZnSO4.7H2O
15 ×
10-5, MnSO4.H2O
2×
10-5, CuSO4.5H2O with pH0 =5, T=55&
#61616
C, N=175 min-1. In this medium, the bacteria produced L-tryptophan at the highest concentration of 0.204 kg m-3 and L-phenylalanine at a maximum concentration of 0.0106 kg m-3 with no L-tyrosine production. Finally the fermentation and oxygen transfer characteristics of the bioprocess were investigated in 3.0 dm3 pilot scale bioreactors. The effects of oxygen transfer were investigated at four different conditions at the parameters air inlet rates of QO/VR =0.2, and 0.5 vvm, and agitation rates of N= 250, 500, 750 min-1. The effect of pH was investigated at pH=5 uncontrolled and controlled operations. The variations in cell, fructose, amino acid and organic acid concentrations with the cultivation time
and using the dynamic method, the oxygen uptake rate and the liquid phase mass transfer coefficient values throughout the growth phase of the bioprocess
the yield and maintenance coefficients were determined. The aromatic amino acids produced at the highest and the least amount and frequency were L-tryptophan and L-tyrosine, respectively. The highest L-tryptophan production, 0.32 kg m-3 in 17 hour was at 0.2 vvm and 500 min-1. Among all operations, the highest L-tryptophan was produced at the lowest oxygen transfer condition. Controlled-pH conditions produced more L-tryptophan.
29
Roberts, Susan Ann. "Aromatic amino acid metabolism in the human, estimation of tyrosine requirement in the neonate and adult." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape9/PQDD_0003/NQ41297.pdf.
Повний текст джерела
30
Gummalla, Sanjay. "Aromatic Amino Acid Catabolism by Lactobacillus spp.: Biochemistry and Contribution to Cheese Flavor Development." DigitalCommons@USU, 2002. https://digitalcommons.usu.edu/etd/5484.
Повний текст джерелаАнотація:
Amino acids derived from the degradation of casein in cheese serve as precursors for the generation of desirable and undesirable flavor compounds. Microbial degradation of aromatic amino acids is associated with the formation of aroma compounds that impart putrid-fecal, barny-utensil, and floral off-flavors in cheese, but pathways for their production had not been established. This study investigated Tyr and Phe catabolism by Lactobacillus casei and Lactobacillus helveticus cheese flavor adjuncts under simulated Cheddar cheese-ripening conditions (pH 5.2, 4% NaCl, 15°C, no sugar). Enzyme assays of cell-free extracts and micellar electrokinetic capillary chromatography of supernatants indicated that L. casei and L. helveticus strains catabolize Tyr and Phe by successive transamination and dehydrogenation reactions. Major products of Tyr and Phe catabolism included off-flavor compounds formed by chemical degradation of the α-keto acids, produced by transamination, and aromatic α-hydroxy acids derived from α-keto acids by α-hydroxy acid dehydrogenases. Action of Lacrococcus lactis aminotransferase enzymes on Trp, Tyr, and Phe also leads to the formation of α-keto acids, but unlike lactobacilli, the former bacteria do not express dehydrogenase activity under cheese-like conditions (pH 5.2, 4% NaCl, 15°C, no sugar). Since aromatic α-keto acids may degrade spontaneously into undesirable flavor compounds, α-hydroxy acid dehydrogenases may be useful in controlling off-flavor development via diversion of chemically labile α-keto acids to more stable a-hydroxy acids. To test this hypothesis, we investigated the effect of D-hydroxyisocaproate dehydrogenase overexpression by a L. casei adjunct on chemical and sensory properties of reduced-fat Cheddar cheese made with and without addition of 20 mM α-ketoglutarate. The D-hydroxyisocaproic acid dehydrogenase gene (D-HicDH) was cloned into a high copy number vector pTRKH2 and transformed into L. casei ATCC334. Reduced-fat Cheddar cheeses were made with Lactococcus lactis starter only, starter + L. casei ATCC334 with pTRKH2, and starter + L. casei ATCC334 with pTRKH2: D-HicDH, and then volatile analysis was performed by gas chromatography and mass spectrometry. Statistical analysis of volatile data after 3 mo of ripening at 7°C showed profiles of ketones, aldehydes, alcohols, esters, sulfur compounds, and benzaldehyde were significantly altered by culture treatments and α-ketoglutarate addition, and these treatments also affected sensory flavor attributes of experimental cheeses. Results also indicated overexpression of D-hydroxyisocaproic acid dehydrogenase can divert labile α-keto acids into more stable compounds, but the overall effect seemed to diminish both beneficial and detrimental flavor notes.
31
Tran, David. "Investigating the substrate specificity of 3-deoxy-D-arabino-heptulosonate 7-phosphate (DAH7P) synthase." Thesis, University of Canterbury. Chemistry, 2011. http://hdl.handle.net/10092/6565.
Повний текст джерелаАнотація:
The shikimate pathway is a biosynthetic pathway that is responsible for producing a variety of organic compounds that are necessary for life in plants and microorganisms. The pathway consists of seven enzyme catalysed reactions beginning with the condensation reaction between D-erythrose 4-phosphate (E4P) and phosphoenolpyruvate (PEP) to give the seven-carbon sugar DAH7P. This thesis describes the design, synthesis and evaluation of a range of alternative non-natural four-carbon analogues of E4P (2- and 3-deoxyE4P, 3-methylE4P, phosphonate analogues of E4P) to probe the substrate specificity of different types of DAH7P synthases [such as Mycobacterium tuberculosis (a type II DAH7PS), Escherichia coli (a type Ialpha DAH7PS) and Pyrococcus furiosus (a type Ibeta DAH7PS)].
32
Graf, Roney. "Anthranilate synthase and chorismate mutase : allosteric regulation of two branchpoint enzymes from the aromatic amino acid biosynthetic pathway of the yeast Saccharomyces cerevisiae /." [S.l.] : [s.n.], 1994. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10724.
Повний текст джерела
33
Picoli, Junior Gilmar José [UNESP]. "Influência do glyphosate no perfil bioquímico e fisiológico de populações de azevém (Lolium multiflorum) suscetíveis e resistentes ao herbicida." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/135868.
Повний текст джерелаАнотація:
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
No Brasil, o azevém (Lolium multiflorum) foi identificado como resistente ao glyphosate se tornando um grande problema em determinadas lavouras. Dessa forma, entender o comportamento a nível bioquímico e fisiológico desta planta daninha são ferramentas que auxiliam num manejo eficiente. Com isso, o objetivo deste trabalho foi comparar o perfil bioquímico e fisiológico de populações de azevém suscetíveis e resistentes ao herbicida glyphosate aplicação do mesmo. Foram realizados quatro estudos em casa-de-vegetação com delineamento experimental inteiramente casualizados com quatro repetições sendo semeadas três populações de azevém (Lolium multiflorum) consideradas como suscetível (S), com suspeita de resistência (R1) e resistente (R2) ao herbicida glyphosate. No primeiro estudo foi obtido o controle aos 21 dias após a aplicação (DAA) e quantificada a massa seca aos 28 DAA das três populações. Os tratamentos foram constituídos da aplicação do herbicida glyphosate composto pelas doses: 0, 135, 270, 540, 1080, 2160, 4320, 8640 g e.a. ha-1. O segundo estudo teve como objetivo determinar a atividade da enzima fenilalanina amônia liase (PAL) nas diferentes populações as 12, 24, 48 e 72 horas após a aplicação (HAA). Os tratamentos foram compostos de duas doses (720 g e.a. ha-1 e 1080 g e.a. ha-1) mais uma testemunha sem aplicação. No terceiro estudo foram realizadas avaliações da fotossíntese nas três populações ao 1, 3, 7 e 28 DAA. As variáveis analisadas foram: taxa de assimilação líquida de CO2, condutância estomática, concentração interna de CO2, transpiração, eficiência do uso da água e eficiência instantânea de carboxilação. Os tratamentos foram compostos de duas doses (720 g e.a. ha-1 e 1080 g e.a. ha-1) mais uma testemunha sem aplicação. O quarto estudo teve o objetivo de quantificar compostos alterados da rota do ácido chiquímico. Para isso, foram utilizados os mesmos tratamentos do primeiro estudo e realizadas coletas das folhas aos 5, 11 e 28 DAA. Os compostos analisados foram: glyphosate, AMPA (ácido aminometilfosfônico), ácido chiquímico, ácido quínico, shiquimato-3-fosfato, os aminoácidos aromáticos fenilalanina, tirosina e triptofano, ácido ferúlico, ácido coumárico e ácido cafeico. Na população considerada resistente, a atividade da enzima fenilalanina amônia liase manteve-se alta após a aplicação do glyphosate. Todas as variáveis fisiológicas foram afetadas após a aplicação do glyphosate nas três populações, porém, R2 foi capaz de se recuperar apresentando valores semelhantes à testemunha. Os níveis de ácido chiquímico e quínico apresentaram padrões semelhantes onde houve aumento para as populações suscetíveis com o aumento da dose do herbicida enquanto que para a resistente os valores se mantiveram semelhantes. Ocorreu aumento dos níveis de shiquimato-3-fosfato para a população R2 se mantendo constante para as suscetíveis. Houve redução dos aminoácidos aromáticos com a aplicação do glyphosate para as populações suscetíveis.
In Brazil, ryegrass (Lolium multiflorum) was identified as resistant to glyphosate becoming a major problem in certain crops. Thus, understanding the behavior of the biochemical and physiological level of this weed are tools that help in efficient management. Thus, the aim of this study was to compare the biochemical and physiological profile of ryegrass populations susceptible and resistant to glyphosate after spray it. Four studies were carried out in greenhouse with experimental design completely randomized with four replications being seeded three populations of ryegrass (Lolium multiflorum) considered as susceptible (S), suspected of having resistance (R1) and resistant (R2) to the herbicide glyphosate. In the first study was measured the control at 21 days after application (DAA) and at 28 DAA, the dry mass the three populations. The treatments consisted of application of the glyphosate composed of doses: 0, 135, 270, 540, 1080, 2160, 4320, 8640 g a.i. ha-1. The second study aimed to determine the phenylalanine ammonia lyase (PAL) activity in different populations at 12, 24, 48 and 72 hours after application (HAA). The treatments consisted of two doses (720 g a.i. ha-1 and 1080 g a.i. ha-1) plus a control without application. In the third study were carried out photosynthesis assessments at three populations at 1, 3, 7 and 28 DAA. The variables analyzed were: CO2 net assimilation rate, stomatal conductance, CO2 internal concentration, transpiration, water use efficiency and instantaneous carboxylation efficiency. The treatments consisted of two doses (720 g a.i. ha-1 and 1080 g a.i. ha-1) plus a control without application. The fourth study aimed to quantify altered compounds of the shikimic acid pathway. For this, the same treatments of the first experiment were used and made collections of leaves at 5, 11, 28 DAA. The compounds analyzed were: glyphosate, AMPA (aminomethylphosphonic acid), shikimic acid, quinic acid, shikimate 3-phosphate, the aromatic amino acids phenylalanine, tyrosine and tryptophan, ferulic acid, coumaric acid and caffeic acid. The phenylalanine ammonia lyase enzyme was not influenced by glyphosate in resitant population. All physiological variables were affected after the application of glyphosate at the three populations, but R2 was able to recover with values similar to the control. The shikimic and quinic acid levels showed similar patterns where, there was an increase for susceptible populations with increasing doses of the herbicide while in resistant, the values remained similar. There was increase in levels of shikimate-3-phosphate to the R2 population, remaining constant for susceptible. There was a reduction of the aromatic amino acids with the application of glyphosate for the susceptible populations.
34
Strittmatter, Axel. "Transcriptional Regulation and Differentiation in Saccharomyces and Aspergillus: jlbA, RPS26, and ARO3/4." Doctoral thesis, [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=970349076.
Повний текст джерела
35
Campbell, Craig D. "Lewis base-promoted organocatalysis : O- to C-carboxyl transfer reactions." Thesis, University of St Andrews, 2010. http://hdl.handle.net/10023/2609.
Повний текст джерелаАнотація:
This work describes the application of a variety of Lewis bases, encompassing predominantly N-heterocyclic carbenes (NHCs), but also the use of imidazoles, aminopyridines, amidines and isothioureas, as effective catalysts in the dearomatisation of heterocyclic carbonates, predominantly the rearrangement of oxazolyl carbonates to their C-carboxyazlactone isomers by means of the Steglich rearrangement. This rearrangement reaction has been investigated extensively, with the development of simplified reaction procedures and the invention of domino cascade protocols incorporating this transformation. In an attempt to understand the mechanism of this O- to C-carboxylation process, a number of interesting observations have been made. Firstly, the class of NHC has an important factor in promoting the rearrangement, with triazolinylidenes being the most effective. Secondly, an interesting chemoselectivity has been delineated using triazolium-derived NHCs, prepared using weak bases (typically Et₃N) or strong metallated bases; both alkyl and aryl oxazolyl carbonates undergo smooth rearrangement with triazolinylidenes derived from strong metallated bases such as KHMDS, while only aryl oxazolyl carbonates undergo rearrangement using Et₃N. Extensive effort has focused towards the development of asymmetric variants of these protocols, primarily towards the design, synthesis and evaluation of chiral NHC precatalysts. To this end, a number of chiral azolium salts have been prepared, encompassing a number of different NHC classes, including C₁- and C₂-imidazolinium salts, C₂-imidazolium salts and a range of triazolium salts. Efforts towards the asymmetric catalysis of the Steglich rearrangement of oxazolyl carbonate substrates have given an optimal 66% ee. Similar rearrangements have been demonstrated with the related furanyl heterocyclic substrate class, producing a mixture of α- and γ-carboxybutenolides. In contrast to the analogous oxazolyl carbonates, the regioselectivity of this rearrangement is dependent upon the nature of the Lewis base employed. Amidines and aminopyridines give a mixture of the α- and γ- regioisomers with generally the α-regioisomer being preferred, while a triazolium-derived NHC gives rise to predominantly the thermodynamically more stable γ-carboxybutenolide. Using amidines or aminopyridines, this rearrangement has been shown to proceed via an irreversible C-C bond-forming process, but in contrast, the rearrangement using the NHC proceeds via an equilibrium process with an optimised regioselectivity of >98:2 for the γ-carboxybutenolide regioisomer over the α-regioisomer. Whilst the asymmetric variant using chiral NHCs has proven unfruitful, rearrangements using a chiral isothiourea have given high levels of regioselectivity towards the α- regioisomer and with excellent levels of enantiodiscrimination (77–95% ee).
36
Mai, Thi thoa. "Nouvelles voies d’accès à des acides alpha-aminés énantioenrichis par mémoire de chiralité ou chiralité gelée." Thesis, Paris 11, 2012. http://www.theses.fr/2012PA112045.
Повний текст джерелаАнотація:
Les acides α-aminés non protéinogènes sont des composés riches d’applications et peuvent donner accès à des composés possédant des propriétés biologiques intéressantes ou à des analogues de peptides. Ainsi, de nombreuses méthodes de synthèse asymétrique ont été développées. Parmi celles-ci, seulement quelques méthodes utilisent la chiralité d’acides α -aminés tertiaires naturels pour accéder à des acides α -aminés quaternaires et il n’existe que peu de synthèses asymétriques absolues d’acides α -aminés tertiaires.Notre équipe a précédemment développé une méthode de synthèse d’acides α-aminés quaternaires reposant sur le concept de la mémoire de chiralité. Cette méthode utilise la chiralité axiale d’amides aromatiques tertiaires pour l’alkylation stéréoselective d’énolates d’acides aminés. Lors de ma thèse, nous avons souhaité appliquer cette méthode d’alkylation stéréosélective d’énolate à d’autres types de réaction tels que la réaction d’aldolisation (utilisant un aldéhyde comme électrophile, et dans ce cas il est nécessaire de contrôler un second centre asymétrique), la réaction d’arylation (utilisant un sel de diaryliodonium comme électrophile) ou à la synthèse totale des composés biologiques intéressants. Des résultats préliminaires encourageants obtenus dans des réactions d’aldolisation (dans le cas avec du benzaldéhyde), d’arylation ainsi que dans la synthèse du précurseur de la L-Méthyl DOPA seront présentés.D’autre part, nous exposerons également la stratégie de synthèse des dérivés d’acides α-aminés tertiaires et des aminoalcools, qui utilise le concept de la chiralité gelée. Cette méthode repose sur l’emploi de la chiralité axiale dynamique des amides aromatiques tertiaires, qui est gelée dans un cristal chiral, et une réaction d’alkylation stéréosélective d’énolate conduisant à des acides aminés énantiomériquement enrichis. En effet, en partant de la glycine, nous avons réussi à trouver un composé de départ qui cristallise dans un groupe d’espace chiral, qui donne donc des cristaux chiraux après la cristallisation. Après avoir trouvé des conditions optimales pour la réaction d’allylation, plusieurs autres électrophiles ont été employés avec succès. Les produits alkylés sont obtenus avec des rendements allant jusqu’à 80% et des excès énantiomériques allant jusqu’à 96% sans utiliser d’autre source de chiralité externe que celle du cristal. L’ouverture de ces composés conduit à la formation des acides α-aminés tertiaires énantiomériquement enrichis. Il s’agit donc d’une synthèse asymétrique absolue d’acides α-aminésNon proteinogenic α-amino acids can lead to compounds which exhibit interesting biological properties, or peptides analogues. Numerous methods for asymmetric synthesis of these compounds have been developed. However, few examples have used the chirality of natural tertiary α-amino acids for the synthesis of quaternary α-amino acids, and few examples of asymmetric absolute synthesis to access to tertiary α -amino acids have been described so far. Our research group has previously developed a synthesis of enantioenriched quaternary α-amino acids, based on memory of chirality and using the axial chirality of tertiary aromatic amides for stereoselective alkylation of an enolate of an amino acid.This thesis focuses on expending this methodology to other type of reactions, for example, aldolisation reactions (using an aldehyde as electrophile, in this case it is necessary to control the second asymmetric center), arylation reactions (using a diaryliodonium salt as electrophile) or to the the total synthesis of compounds exhibiting interesting biological properties. Herein, we will show our preliminary results in aldolisation reactions (with benzaldehyde), in arylation reactions and also in the total synthesis of L-Methyl DOPA.On the other hand, we will also present an enantioselective synthesis of tertiary α-amino acids derivatives and of amino alcohols based on the principle of frozen chirality. The strategy uses the dynamic axial chirality of tertiary aromatic amides, which is frozen in chiral crystal, and a stereoselective alkylation reaction of enolate leads to enantioenriched α-amino acids. A compound synthesized from glycine has been finally selected to optimise the asymmetric allylation reaction. These optimales conditions were then successfully employed with various electrophiles. Alkylated products were obtained in yield up to 80% and enantiomeric excesses up to 96% using only chirality of crystal. The deprotection of alkylated products leads to the formation of enantienriched α-amino acids
37
Demonchaux, Patrice. "Recherche d'agents radioprotecteurs : synthèse et mécanisme d'action de composés de type intercalant-aminothiol." Grenoble 1, 1988. http://www.theses.fr/1988GRE10016.
Повний текст джерелаАнотація:
Les intercalants utilises sont des amino-9 chloro-6 methoxy-2 acridines des amino-4 chloro-7 quinoleines et des amino-4 chloro-7 methyl-1 quinoleiniums sur lesquels ont ete introduites des chaines analogues a celles de la cysteamine et du wr 2727; etude de l'affinite de ces composes avec l'adn
38
Schreiter, Katja. "Aminosäurefunktionalisierte Chromophore als solvatochrome Sondenmoleküle." Doctoral thesis, Universitätsbibliothek Chemnitz, 2010. http://nbn-resolving.de/urn:nbn:de:bsz:ch1-qucosa-62805.
Повний текст джерелаАнотація:
In der vorliegenden Arbeit wird die Synthese und Charakterisierung von chiralen prolylfunktionalisierten Farbstoffen vorgestellt. Als chromophore Schlüsselverbindungen wurden Nitroaniline aber auch größere push-pull pi-Systeme wie Schiffsche Basen, Azofarbstoffe und Merocyanine gewählt. Im Fokus dieser Arbeit stehen dabei deren solvatochrome Eigenschaften, pH-Sensitivität sowie mögliche Wechselwirkung mit Biomolekülen und verschiedenen An- und Kationen. Zusätzlich erfolgten Umsetzungen ausgewählter prolylfunktionalisierter chromophorer Bausteine zu Estern und Amiden. Der Einfluss des Prolylbausteins auf das im Festkörper ausgebildete Wasserstoffbrückenbindungsmusters wurde über Einkristallröntgenstrukturanalysen untersucht und nach der Graph Set Methode von Etter klassifiziert. Neben der Einkristallröntgenstrukturanalyse erfolgte die weitere Untersuchung der Festkörpereigenschaften mit Hilfe von UV/Vis- sowie NMR-spektroskopischen Methoden. Das solvatochrome Verhalten der prolylfunktionalisierten Verbindungen wurde mittels multipler linearer Regressionsanalyse gemäß der LSER- (linear solvation energy relationship) Beziehung nach den Ansätzen von Kamlet-Taft und Catalán beschrieben und vergleichend interpretiert.
39
Hesse, Almut. "Entwicklung immunchemischer Methoden zur Spurenanalytik der Sprengstoffe Nitropenta und Trinitrotoluol." Doctoral thesis, Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät, 2017. http://dx.doi.org/10.18452/17773.
Повний текст джерелаАнотація:
Der Sprengstoff PETN ist äußerst schwer zu detektieren. Ein verbesserter anti-PETN-Antikörper wurde durch Anwendung des Bioisosterie-Konzepts entwickelt. Diese polyklonalen IgGs sind sehr selektiv und sensitiv. Die Nachweisgrenze des ELISAs beträgt 0,15 µg/L. Der Messbereich des Immunoassays liegt zwischen 1 und 1000 µg/L. Die Antikörper sind recht pH-stabil als auch robust gegen Lösungsmittelzusätze. Für die Umweltanalytik von TNT wurde eine HPLC-kompatible Affinitätssäule mit porösem Glas als Trägermaterial hergestellt. Um die anti-TNT-Antikörper selektiv aus den TNT-Seren zu isolieren, wurde eine Trennung an einer Dinitrophenyl-Affinitätssäule durchgeführt. Zur Optimierung der Kopplungsmethode wurden orangefarbene Dabsyl-Proteine synthetisiert und auf der Oberfläche gebunden. Die Färbung wurde als Indikator für die Ligandendichte verwendet. Wegen der hohen Affinitätskonstanten der anti-TNT-IgGs lässt sich TNT nicht reversibel von der TNT-Affinitätssäule eluieren. Daher wurde eine neuartige Elutionsmethode entwickelt, die thermische Online-Elution. Die maximale Kapazität einer TNT- Affinitätssäule betrug 650 ng TNT bzw. 10 µg/mL Säulenvolumen. Um die Ligandendichte der TNT-Affinitätssäulen zu bestimmen, wurde ein neues Verfahren entwickelt, da die spektroskopischen Proteinbestimmungsmethoden nicht geeignet waren. Zur Proteinbestimmung wurde eine HPLC-Trennung der Aminosäuren Tyr und Phe ohne vorherige Derivatisierung entwickelt. Die Proteinhydrolysezeit wurde durch Einsatz einer Mikrowelle von 22 h auf 30 min verkürzt. Zur internen Kalibrierung wurden HTyr und FPhe verwendet. Die Nachweisgrenze bei 215 nm ist sowohl für Tyr als auch für Phe 0,05 µM (~ 10 µg/L). Dieses neue Verfahren, das als Aromatische Aminosäureanalyse (AAAA) bezeichnet werden kann, wurde zur Proteinbestimmung von homogenen Proben mit NIST-BSA validiert, wobei die Nachweisgrenze für Proteine 16 mg/L (~ 300 ng BSA) ist. Die relative Standardabweichung incl. der Hydrolysestufe beträgt 5%.The explosive Pentaerythritol tetranitrate (PETN) is extremely difficult to detect. An improved antibody against PETN was developed by using the bioisosteric concept. These polyclonal antibodies are highly selective and sensitive. The limit of detection (LOD) of the ELISA was determined to be 0.15 µg/L. The dynamic range of the assay was found to be between 1 and 1000 µg/L. The antibodies are sufficiently pH-stable and resistant to solvent additives. An HPLC-compatible TNT-affinity column with porous glass as support material was prepared for the environmental analysis. In order to isolate the anti-TNT antibodies of the TNT sera a separation was carried out on a dinitrophenyl-affinity column. To optimize the immobilization method, orange-coloured dabsyl proteins were synthesized and bound to the surface. The colour intensity was found to be an indicator for the immobilization rate. In consequence of the high affinity constants of the anti-TNT antibodies, TNT can''t elute by a typical acidic elution step. Therefore, a novel separation approach, the thermal online-elution was developed. The maximum capacity of an affinity column was 650 ng TNT or 10 µg/mL of column volume. To quantify the immobilization rate of proteins, a new method has been developed, because the usual protein determination methods were unsuitable. Therefore an HPLC separation method of Tyr and Phe was developed without prior derivatization. Two internal standard compounds, HTyr and FPhe, were used for calibration. The LOD was estimated to be 0.05 µM (~ 10 µg/L) for Tyr and Phe at 215 nm. The protein hydrolysis time was reduced from 22 h to 30 min using microwave technique. This procedure, that was termed aromatic amino acid analysis (AAAA), has been validated for protein determination of homogeneous samples with NIST-BSA. The LOD for proteins was calculated to be below 16 mg/L (~ 300 ng BSA absolute). The relative standard deviation, including the hydrolysis step, is 5%.
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Chang, Tung-Ming, and 張通銘. "Aromatic L-Amino Acid Decarboxylase deficiency studied with [18F]fluorodopa PET." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/74269426133424710311.
Повний текст джерелаАнотація:
碩士長榮大學
醫學研究所
97
Objective: Although the symptomatology of aromatic L-Amino acid decarboxylase (AADC) deficiency has been well documented, the cerebral pathogenesis of this disorder is still unknown. Methods: We used [18F]fluorodopa (FDOPA) PET to compare the presynaptic dopamine synthesis capacity in the striatum of six AADC deficient children and five non-AADC deficient children. Caudate and putamen FDOPA PET uptake values were measured and expressed as striatal-to-occipital ratio (SOR) and ratio R defined as SOR-1. Results: A conventional region of interest (ROI) analysis revealed that FDOPA uptake (SOR) in the caudate and putamen was significantly lower in the AADC deficient group than in the control group. The mean SOR of FDOPA uptake value in the caudate nucleus was 51% (p<0.005) and in the putamen 54% (p<0.005) of the control mean values.( 20% and 19% for ratio R, respectively ) Conclusions: We confirm the presynaptic nigrostriatal dopaminergic hypofunction in AADC deficient children which results in lower levels of biogenic amine neurotransmitters and associated neurological symptoms. This work further has demonstrated that FDOPA PET may serve as a method to investigate the cerebral dopaminergic abnormality in AADC deficient children.
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Tsai, Chi-Ren, and 蔡啟仁. "Genetic Analysis and Aberrant Splicing Modulation in Aromatic L-amino Acid Decarboxylase Deficiency." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/46152624575849436415.
Повний текст джерелаАнотація:
博士國立中興大學
分子生物學研究所
105
Aromatic L-amino acid decarboxylase deficiency (AADCD), attributed to mutations in the dopa decarboxylase (DDC) gene, is a rare neurometabolic disease resulting from a defect in the biosynthesis of dopamine and serotonin. In this study, we demonstrated that DDC c.714+4 A>T is a splicing mutation and found the DDC c.714+4 A>T mutation is the most prevalent mutation among Taiwanese AADCD. Haplotype analysis indicated that c.714+4 A>T alleles possessed a founder mutation among Taiwanese patients. In addition, the molecular consequences and function of the DDC c.714+4 A>T mutation were examined in AADCD patient-derived lymphoblastoid cells. We identified novel DDC mRNA isoforms spliced with a new exon (exon 6a) in normal and c.714 +4 A>T lymphoblastoid cells. We also identified the SR proteins SRp30c and SRp55, as well as cis-elements involved in modulating the splicing of this mutated transcript. Notably, we demonstrated that antisense oligonucleotides (ASOs) were able to restore the normal mRNA splicing and increase the level of DDC protein, as well as its downstream product serotonin, in lymphoblastoid cells derived from patients with AADCD, suggesting that these ASOs might represent a feasible alternative strategy for gene therapy of AADCD in patients with the common c.714 +4 A>T mutation.
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Shih, De-Fen, and 史德芬. "Aromatic L-amino Acid Decarboxylase (AADC) is Crucial for Brain Development and Motor Functions." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/82105246573417562362.
Повний текст джерелаАнотація:
博士國立臺灣大學
生命科學系
104
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. Whole-mount in situ hybridization analysis showed that the aadc gene was specifically expressed in the epiphysis, locus coeruleus, dipencephalic catecholaminergic (DC) clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of AADC by the inhibitor NSD-1015 or anti-sense morpholino (MO) led to a reduction brain volume and body length. There was an increased apoptosis occurrence in the brain and a loss of DC cluster neurons in AADC morphants (aadc MO-injected embryos). Seizure-like activity was also detected in AADC morphants in a dose-dependent manner. The AADC morphants were less sensitive in touch response and had a reduced swimming activity, and these phenotypes were rescued by injection of aadc plasmids. In conclusion, inhibition of AADC may reduce brain size, increase apoptosis, and reduce motor function in zebrafish. Zebrafish can be a useful model for investigating the pathogenetic mechanisms of AADC deficiency in children.
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Liu, Chi-Ju, and 柳紀如. "Studies on the Analysis of Neurotansmitter Metabolites for Aromatic L- Amino Acid Decarboxylase Deficiency." Thesis, 2014. http://ndltd.ncl.edu.tw/handle/80667714309399618071.
Повний текст джерелаАнотація:
碩士中臺科技大學
醫學檢驗生物技術系碩士班
102
Aromatic L-Amino Acid Decarboxylase (AADC) is one of the 201 kinds of rare diseases in the Health Promotion Administration of Ministry of Health and Welfare announcement, which belongs to the amino acid / organic acid metabolism disorders. The position on chromosome 7 of AADC gene p12 mutation causes serious AADC enzyme activity decrease, when AADC deficiency or the concentration is enough will lead to L-Dopa and 5-HTP can not convert into dopamine and serotonin, making the levels of dopamine、serotonin、Epinephrine and Norepinephrine go down, resulting in a variety of disorders of psychomotor Modulation, maladjustment in sleep pattern, body temperature，cardiovascular, respiratory and gastrointestinal systems. In this study, The AADC neurotransmitter substances related metabolic intermediate Tryptophan、5-HTP、Serotonin、5-HIAA、MHPG were separated on a XbridgeTM C18,3.5 μm, 4.6 × 150 mm, using a 0.1% (v / v) 2.651 M formic acid - acetonitrile elution solution with an Agilent 1100 Liquid Chromatographic System consisting series connection UV detector and fluorescence detector. Analysis were carried out at fluorescence detector excitation wavelength 280 nm, emission wavelength 320 nm and ultraviolet wavelength 280 nm. The separation flow rate is 0.4 ml / min and the injection volume of analyte 20μl. Calibration curves were linear over the 5-200ng/ml for Tryptophan、5-HTP、Serotonin、5-HIAA、MHPG that alhaving a good linear relationship. A careful solid-phase extraction procedure was developed for the pre-treatment of urine and plasma samples. Tryptophan, 5-HTP, Serotonin, 5-HIAA, MHPG recovery FD (UV) were 57％ (84%), 83% (102%), 82% (102%), 57% (73%) , 71% (86%) respectively.
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Chung, Yu-Chien, and 鍾宇謙. "Molecular Cloning of Aromatic L-Amino Acid Decarboxylase Gene from Xanthobacter autotrophicus Py2, and Enzyme Characterization." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/33474584175600252411.
Повний текст джерелаАнотація:
碩士大葉大學
分子生物科技學系碩士班
97
Aromatic L-amino acid decarboxylase ( AADC; EC 4.1.1.28 ) catalyses the conversion of L-3,4-dihydroxyphenylalanine ( Levodopa; L-DOPA ) to dopamine. Clinically, medical treatment for parkinson’s disease ( PD ) is using the chemically synthetic L-DOPA and dopamine, but that has side effects. So searching for the natural source is becoming more significant and necessary. In our study, AADC gene in the chromosome of Xanthobacter autotrophicus Py2 with the size of 1,425 bp was significantly ligated with pQE30 expression vector and then transformed into E. coli Nova Blue for overexpression. The gene expressed the peptide chain AADC with the molecular weight of 51 kDa. This protein was isolated by 6 His-tag and assayed by TNB ( 2, 4, 6-Trinitrobenzene 1-sulfonic acid ) reagent method in finding activity of the enzyme. After initial incubation of the AADC enzyme at 42 ℃ with 2.5 mM L-DOPA for 15 mins, this solution was added with TNB reagent for further 15 mins. The tube added with toluene was vortexed and centrifuged to separate the top layer of TNP-dopamine ( Trinitrophenyl dopamine ) from the bottom layer of TNP-DOPA ( Trinitrophenyl DOPA ) and then the concentration of TNP-dopamine was determined spectrophotometerically. Following the course, we selected three clones with lower level activity have the same mutation with Q219H from 40 screened clones. In the first screening, we didn’t find higher activity so that we changed medium to BHI ( Brain heart infusion ) because BHI is more nutrition for screening higher activity. In the second screening of 40 clones, we found two clones with L325Q and L400R for lower activity, but R406H for higher activity. By the way, we found L400R have growth retardation. Standard curve was made by dopamine reacting with TNB reagent derivation at a high rating of R2 = 0.999 for quantitative determination of AADC enzyme activity. Another standard curve is BSA with Bio-Rad assay for protein quantity. The wild type of AADC enzyme had optimal reaction under 65 mM boric acid pH 8.0 at 42 ℃ which was catalyzing 2.5 mM L-DOPA in 15 mins. The result of specific activity, Km = 209.64 ( μM ), Vmax = 37.17 ( μM / min ), Kcat = 3.8 x 10-3 ( S-1 ) and Kcat / Km = 1.8 x 10-5 were determined . Q219H and L325Q mutants were compared with wild type and resulted in decrease of ( Kcat / Km ) in activity by more than 2.4 and 18 fold for equal quantitative enzyme, respectively. We also added PLP ( Pyridoxal-5`-phosph- ate ) of AADC cofactor that can activate substrate binding more stronger even if original AADC has high activity. The enzymatic activity was increased in 2 fold for purified wild type AADC. However, R406H has lower Km value. These results indicate that both the chemical properties and the shape of these residues are essential for substrate binding in the enzyme catalysis. In addition, the active site of pig kidney AADC was known of H192Q, T246A and K303A, so as found residues at H180, T238 and K295 in the sequence of X. autotrophicus AADC. A null mutant T238A was made, however, its activity was not detectable. Besides, we tried to recovery protein again for mutant L400R using more than one fold LB as culture medium. L400R mutant enzyme was purified, however, its activity was not detectable. We observed modeling of AADC of pig kidney active center is similar to X. autotrophicus AADC. According to modeling of structure from pig kidney active center, corresponding L400R was found very close to the active center. Other mutant AADC, Q219H, L325Q and R406H were on the peripheral of entrance in the active center that might change the original amino acid and influenced substrate binding for AADC activity. In this study, data suggest L400R and T238A are catalytically important active center of X. autotrophicus AADC.
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Rossignoli, Giada. "Aromatic amino acids decarboxylase and histidine decarboxylase: deep functional investigations give insights into pathophysiological mechanisms with possible therapeutic implications." Doctoral thesis, 2019. http://hdl.handle.net/11562/995224.
Повний текст джерелаАнотація:
Aromatic amino acids decarboxylase and histidine decarboxylase (AADC and HDC) are two homologous enzymes responsible for the synthesis of dopamine/serotonin and histamine, respectively, and other minor signalling aromatic amines. All these molecules are main protagonists or regulators of several physiological pathways, which are fundamental both in central nervous system and in peripheral tissues. Alterations of their homeostasis, indeed, as well as of AADC and HDC functioning or expression, cause and/or participate in the development and progression of several often severe and disabling pathological conditions, such as AADC Deficiency and cholangiocarcinoma. Consequently, AADC and HDC characterization might be useful in the pathophysiological understanding of several diseases and in improving/developing new therapeutic strategies. However, the knowledge of the biochemical features of these two crucial enzymes is still rather limited. Thus, the aim of this thesis is to biochemically characterise human HDC, mostly unknown, and to individuate some possible regulative mechanisms for both HDC and AADC. In addition, a neuronal AADC Deficiency cell model, derived from patient induced pluripotent stem cells (iPSCs), was used to evaluate endogenous AADC features, as well as to research further alterations in dopaminergic pathway. Investigations on human recombinant HDC allowed to discover that, surprisingly, its conformation and catalytic efficiency are influenced by redox state: increasing oxidizing conditions, indeed, favour a more stable and active form of the dimeric enzyme, due to the presence of an intermolecular reversible disulphide bridge involving residue Cys180 of both subunits. Then, in solution analyses of a possible phosphorylation of AADC identified Ser193 as protein kinase A target site, and allowed the detection of an effect on enzyme kinetic parameters, in particular an increased affinity for its substrates. Finally, endogenous AADC levels analyses in dopaminergic neurons derived from AADC Deficiency patients suggested a possible positive feedback mechanism that could tend to increase AADC expression, and the same cell model showed alterations in other cell types besides neurons, in particular glia cells, suggesting that variations in neurons-glia cells Abstract 5 interplay could participate in the pathophysiology mechanisms of AADC Deficiency. Altogether, data and information obtained from the performed experiments have increased AADC and HDC knowledge, as well as paved the way for new hypothesis regarding possible efforts in the development of new disease treatments.
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bisello. "HUMAN AROMATIC L-AMINO ACID DECARBOXYLASE: WHEN STRUCTURE AND MOBILITY DRIVE EFFICIENT CATALYSIS. IMPLICATIONS FOR AADC DEFICIENCY." Doctoral thesis, 2021. http://hdl.handle.net/11562/1045846.
Повний текст джерелаАнотація:
L’enzima Decarbossilasi degli L-amino acidi aromatici (AADC) è responsabile della sintesi di due neurotrasmettitori essenziali: la dopamina e la serotonina. AADC deve la sua attività catalitica alla chimica del suo cofattore, il piridossale 5’-fosfato (PLP). La struttura cristallografica dell’enzima da mammifero (precisamente da maiale che ha il 90% di identità con l’enzima umano) nella sua forma olo venne risolta venti anni fa e tale risoluzione aprì la strada ad importanti studi strutturali. Dieci anni dopo venne pubblicata la struttura umana di AADC nella sua forma apo evidenziando quali cambiamenti conformazionali avvengono quando il PLP viene legato dall’enzima. Le strutture apo e olo AADC hanno avuto notevole importanza per la comprensione della patogenicità di varianti enzimatiche associate alla malattia chiamata ‘Deficit da AADC’ (AADCd, OMIM#608643). Questa malattia autosomica recessiva molto rara è dovuta prevalentemente a mutazioni missenso sul gene AADC. I pazienti affetti da AADCd mostrano un’amAromatic L-Amino Acid Decarboxylase (AADC) is the enzyme responsible for the synthesis of two essential neurotransmitter dopamine and serotonin from L-Dopa and L-hydroxytryptophan. AADC owes its specific catalytic activity to the chemistry of its cofactor, pyrydoxal-5’-phosphate (PLP). Almost 20 years ago, the crystal structure of a mammalian holoAADC (porcine, sharing 90% of sequence identity) was solved and the availability of its 3D structure paved the way to structural studies. Moreover, 10 years later, human apoAADC structure was published, shedding light on the conformational rearrangement occurring on the apo enzyme upon addition of PLP. Importantly, apo and holoAADC structures provided crucial insights for the comprehension of the pathogenicity of a number of AADC deficiency associated variants. AADC deficiency (OMIM#608643) is a rare autosomal recessive inborn disease due to missense mutations in the AADC gene. Patients bearing these mutations show mild to severe phenotypes, whose destiny is often fatal. Due to the rarity of the disease and to the heterogeneous response to the treatments, medications are not often satisfactory. In the past years, some efforts on human recombinant AADC pathogenic variants have tried to provide support to the research on AADC deficiency by means of biochemical and biophysical approaches determining the impact of the amino acid substitutions on the enzyme features. Here, a further contribution to the comprehension of the AADC deficiency is provided. The crystal structure of human holoAADC has been solved under different conditions, both in its native and ligand bound form. The combination of crystallographic studies, molecular dynamics simulations (MD) and site directed mutagenesis uncovered novel aspects of the AADC structure-function relationship. Moreover, the characterization of 21 novel identified pathogenic variants (spread on each AADC domain, N-terminal, Large and C-terminal Domains) led to the widening of the range of enzymatic phenotypes associated to AADC deficiency. The proposed combination of biochemical and kinetic studies permitted to determine correlations between structural and functional signals. Enzymatic phenotypes span from variants characterized by a mild phenotypes to variants (mainly located at the NTD-CTD interface) whose dramatic structural defects lead to a catalytic incompetence. In addition, MD simulations and in solutions data point out a critical role for the loop3 element that contains the essential catalytic residue Tyr332. A group of variants affecting loop3 has been identified as catalytically incompetent and their structural features have been dissected thanks also to the solving of the crystal structure of pathogenic variant L353P, which constitutes the first solved structure of an AADC variant. Altogether, this study on human AADC provides new elements for the comprehension of the structure-function relationship of AADC with a particular focus on protein dynamics and mobility. Lastly, structural details might represent the basis for both the designing of novel specific inhibitors and for a better comprehension of the molecular aspects of the variants associated with the AADC deficiency.
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莊東憬. "Significance of L-aromatic amino acid decarboxylase activities on brain levels of the neurotransmitters catecholamine and 5-hydroxytryptamine." Thesis, 1988. http://ndltd.ncl.edu.tw/handle/67971810234604950133.
Повний текст джерела
48
El, Aribi Houssain. "Examination of fragmentations of protonated and metallated amino acids, oligopeptides, and their building blocks using triple quadrupole mass spectrometry /." 2003. http://wwwlib.umi.com/cr/yorku/fullcit?pNQ99165.
Повний текст джерелаАнотація:
Thesis (Ph.D.)--York University, 2003. Graduate Programme in Chemistry.Typescript. Includes bibliographical references. Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://wwwlib.umi.com/cr/yorku/fullcit?pNQ99165
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Hsu, Jean Wei-Chen. "Aromatic amino acid requirements and metabolism /." 2006. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=442583&T=F.
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50
Yuan, Lun-Hsiang, and 袁倫祥. "Photolysis Quantum Yield of Aromatic Amino Acid in the UV range." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/77304565962770993957.
Повний текст джерела