Relevant bibliographies by topics / Coenzyme A Ligases

Contents

  1. Journal articles
  2. Dissertations / Theses
  3. Book chapters

Academic literature on the topic 'Coenzyme A Ligases'

Author: Grafiati
Published: 4 June 2021
Last updated: 1 February 2022

Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles

Select a source type:

Consult the lists of relevant articles, books, theses, conference reports, and other scholarly sources on the topic 'Coenzyme A Ligases.'

Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.

You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.

Journal articles on the topic "Coenzyme A Ligases"

1

Villemur, Richard. "Coenzyme A ligases involved in anaerobic biodegradation of aromatic compounds." Canadian Journal of Microbiology 41, no. 10 (October 1, 1995): 855–61. http://dx.doi.org/10.1139/m95-118.

Full text
Abstract:
Bacterial strains and consortia of bacteria have been isolated for their ability to degrade, under anaerobic conditions, homocyclic monoaromatic compounds, such as phenolic compounds, methylbenzenes, and aminobenzenes. As opposed to aerobic conditions where these compounds are degraded via dihydroxyl intermediates introduced by oxygenases, most of aromatic compounds under anaerobic conditions are metabolized via aromatic acid intermediates, such as nitrobenzoates, hydroxybenzoates, or phenylacetate. These aromatic acids are then transformed to benzoate before the reduction and the cleavage of the benzene ring to aliphatic acid products. One step of these catabolic pathways is the addition of a coenzyme A (CoA) residue to the carboxylic group of the aromatic acids by CoA ligases. This addition would facilitate the enzymatic transformation of the aromatic acids to benzoyl-CoA and the subsequent degradation steps of this latter molecule. Aromatic acid – CoA ligases have been characterized or detected from several bacterial strains that were grown under anaerobic conditions and from an anaerobic syntrophic consortium. They are also involved in the degradation of some aromatic compounds under aerobic conditions. They have molecular masses varying between 48 and 61 kDa, require ATP, Mg2+, and CoASH as cofactors, and have an optimum pH of 8.2–9.3. Amino acid sequence analyses of four aromatic acid–CoA ligases have revealed that they are related to an AMP-binding protein family. Aromatic acid – CoA ligases expressed in anaerobically grown bacterial cells are strictly regulated by the anaerobic conditions and the presence of aromatic acids.Key words: aromatic compounds, coenzyme A ligase, anaerobic microorganisms.
APA, Harvard, Vancouver, ISO, and other styles
2

Altenschmidt, U., B. Oswald, and G. Fuchs. "Purification and characterization of benzoate-coenzyme A ligase and 2-aminobenzoate-coenzyme A ligases from a denitrifying Pseudomonas sp." Journal of Bacteriology 173, no. 17 (1991): 5494–501. http://dx.doi.org/10.1128/jb.173.17.5494-5501.1991.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Horrobin, David F., and Crispin N. Bennett. "Fatty acid coenzyme a ligases as candidate genes in schizophrenia." Schizophrenia Research 41, no. 1 (January 2000): 99. http://dx.doi.org/10.1016/s0920-9964(00)90540-1.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

Di Gioia, Diana, Michelle Peel, Fabio Fava, and R. Campbell Wyndham. "Structures of Homologous Composite Transposons Carrying cbaABC Genes from Europe and North America." Applied and Environmental Microbiology 64, no. 5 (May 1, 1998): 1940–46. http://dx.doi.org/10.1128/aem.64.5.1940-1946.1998.

Full text
Abstract:
ABSTRACT IS1071 is a class II transposable element carrying atnpA gene related to the transposase genes of the Tn3 family. Copies of IS1071 that are conserved with more than 99% nucleotide sequence identity have been found as direct repeats flanking a remarkable variety of catabolic gene sequences worldwide. The sequences of chlorobenzoate catabolic transposons found on pBRC60 (Tn5271) in Niagara Falls, N.Y., and on pCPE3 in Bologna, Italy, show that these transposons were formed from highly homologous IS1071 and cbaABCcomponents (levels of identity, >99.5 and >99.3%, respectively). Nevertheless, the junction sequences between the IS1071Land IS1071R elements and the internal DNA differ by 41 and 927 bp, respectively, suggesting that these transposons were assembled independently on the two plasmids. The formation of the right junction in both transposons truncated an open reading frame for a putative aryl-coenzyme A ligase with sequence similarity to benzoate- andp-hydroxybenzoate-coenzyme A ligases ofRhodopseudomonas palustris.
APA, Harvard, Vancouver, ISO, and other styles
5

Nolte, Johannes Christoph, Marc Schürmann, Catherine-Louise Schepers, Elvira Vogel, Jan Hendrik Wübbeler, and Alexander Steinbüchel. "Novel Characteristics of Succinate Coenzyme A (Succinate-CoA) Ligases: Conversion of Malate to Malyl-CoA and CoA-Thioester Formation of Succinate AnaloguesIn Vitro." Applied and Environmental Microbiology 80, no. 1 (October 18, 2013): 166–76. http://dx.doi.org/10.1128/aem.03075-13.

Full text
Abstract:
ABSTRACTThree succinate coenzyme A (succinate-CoA) ligases (SucCD) fromEscherichia coli,Advenella mimigardefordensisDPN7T, andAlcanivorax borkumensisSK2 were characterized regarding their substrate specificity concerning succinate analogues. Previous studies had suggested that SucCD enzymes might be promiscuous toward succinate analogues, such as itaconate and 3-sulfinopropionate (3SP). The latter is an intermediate of the degradation pathway of 3,3′-dithiodipropionate (DTDP), a precursor for the biotechnical production of polythioesters (PTEs) in bacteria. ThesucCDgenes were expressed inE. coliBL21(DE3)/pLysS. The SucCD enzymes ofE. coliandA. mimigardefordensisDPN7Twere purified in the native state using stepwise purification protocols, while SucCD fromA. borkumensisSK2 was equipped with a C-terminal hexahistidine tag at the SucD subunit. Besides the preference for the physiological substrates succinate, itaconate, ATP, and CoA, high enzyme activity was additionally determined for both enantiomeric forms of malate, amounting to 10 to 21% of the activity with succinate.Kmvalues ranged from 2.5 to 3.6 mM forl-malate and from 3.6 to 4.2 mM ford-malate for the SucCD enzymes investigated in this study. Asl-malate-CoA ligase is present in the serine cycle for assimilation of C1compounds in methylotrophs, structural comparison of these two enzymes as members of the same subsubclass suggested a strong resemblance of SucCD tol-malate-CoA ligase and gave rise to the speculation that malate-CoA ligases and succinate-CoA ligases have the same evolutionary origin. Although enzyme activities were very low for the additional substrates investigated, liquid chromatography/electrospray ionization-mass spectrometry analyses proved the ability of SucCD enzymes to form CoA-thioesters of adipate, glutarate, and fumarate. Since all SucCD enzymes were able to activate 3SP to 3SP-CoA, we consequently demonstrated that the activation of 3SP is not a unique characteristic of the SucCD fromA. mimigardefordensisDPN7T. The essential role ofsucCDin the activation of 3SPin vivowas proved by genetic complementation.
APA, Harvard, Vancouver, ISO, and other styles
6

Bhushan, Alok, Rajinder Pal Singh, and Inderjit Singh. "Characterization of rat brain microsomal acyl-coenzyme A ligases: Different enzymes for the synthesis of palmitoyl-coenzyme A and lignoceroyl-coenzyme A." Archives of Biochemistry and Biophysics 246, no. 1 (April 1986): 374–80. http://dx.doi.org/10.1016/0003-9861(86)90482-0.

Full text
APA, Harvard, Vancouver, ISO, and other styles
7

Coleman, James P., L. Lynn Hudson, Susan L. McKnight, John M. Farrow, M. Worth Calfee, Claire A. Lindsey, and Everett C. Pesci. "Pseudomonas aeruginosa PqsA Is an Anthranilate-Coenzyme A Ligase." Journal of Bacteriology 190, no. 4 (December 14, 2007): 1247–55. http://dx.doi.org/10.1128/jb.01140-07.

Full text
Abstract:
ABSTRACT Pseudomonas aeruginosa is an opportunistic human pathogen which relies on several intercellular signaling systems for optimum population density-dependent regulation of virulence genes. The Pseudomonas quinolone signal (PQS) is a 3-hydroxy-4-quinolone with a 2-alkyl substitution which is synthesized by the condensation of anthranilic acid with a 3-keto-fatty acid. The pqsABCDE operon has been identified as being necessary for PQS production, and the pqsA gene encodes a predicted protein with homology to acyl coenzyme A (acyl-CoA) ligases. In order to elucidate the first step of the 4-quinolone synthesis pathway in P. aeruginosa, we have characterized the function of the pqsA gene product. Extracts prepared from Escherichia coli expressing PqsA were shown to catalyze the formation of anthraniloyl-CoA from anthranilate, ATP, and CoA. The PqsA protein was purified as a recombinant His-tagged polypeptide, and this protein was shown to have anthranilate-CoA ligase activity. The enzyme was active on a variety of aromatic substrates, including benzoate and chloro and fluoro derivatives of anthranilate. Inhibition of PQS formation in vivo was observed for the chloro- and fluoroanthranilate derivatives, as well as for several analogs which were not PqsA enzymatic substrates. These results indicate that the PqsA protein is responsible for priming anthranilate for entry into the PQS biosynthetic pathway and that this enzyme may serve as a useful in vitro indicator for potential agents to disrupt quinolone signaling in P. aeruginosa.
APA, Harvard, Vancouver, ISO, and other styles
8

El-Said Mohamed, Magdy. "Biochemical and Molecular Characterization of Phenylacetate-Coenzyme A Ligase, an Enzyme Catalyzing the First Step in Aerobic Metabolism of Phenylacetic Acid inAzoarcus evansii." Journal of Bacteriology 182, no. 2 (January 15, 2000): 286–94. http://dx.doi.org/10.1128/jb.182.2.286-294.2000.

Full text
Abstract:
ABSTRACT Phenylacetate-coenzyme A ligase (PA-CoA ligase; AMP forming, EC6.2.1.30 ), the enzyme catalyzing the first step in the aerobic degradation of phenylacetate (PA) in Azoarcus evansii, has been purified and characterized. The gene (paaK) coding for this enzyme was cloned and sequenced. The enzyme catalyzes the reaction of PA with CoA and MgATP to yield phenylacetyl-CoA (PACoA) plus AMP plus PPi. The enzyme was specifically induced after aerobic growth in a chemically defined medium containing PA or phenylalanine (Phe) as the sole carbon source. Growth with 4-hydroxyphenylacetate, benzoate, adipate, or acetate did not induce the synthesis of this enzyme. This enzymatic activity was detected very early in the exponential phase of growth, and a maximal specific activity of 76 nmol min−1mg of cell protein−1 was measured. After 117-fold purification to homogeneity, a specific activity of 48 μmol min−1 mg of protein−1 was achieved with a turnover number (catalytic constant) of 40 s−1. The protein is a monomer of 52 kDa and shows high specificity towards PA; other aromatic or aliphatic acids were not used as substrates. The apparent Km values for PA, ATP, and CoA were 14, 60, and 45 μM, respectively. The PA-CoA ligase has an optimum pH of 8 to 8.5 and a pI of 6.3. The enzyme is labile and requires the presence of glycerol for stabilization. The N-terminal amino acid sequence of the purified protein showed no homology with other reported PA-CoA ligases. The gene encoding this enzyme is 1,320 bp long and codes for a protein of 48.75 kDa (440 amino acids) which shows high similarity with other reported PA-CoA ligases. An amino acid consensus for an AMP binding motif (VX2SSGTTGXP) was identified. The biochemical and molecular characteristics of this enzyme are quite different from those of the isoenzyme catalyzing the same reaction under anaerobic conditions in the same bacterium.
APA, Harvard, Vancouver, ISO, and other styles
9

Egland, P. G., J. Gibson, and C. S. Harwood. "Benzoate-coenzyme A ligase, encoded by badA, is one of three ligases able to catalyze benzoyl-coenzyme A formation during anaerobic growth of Rhodopseudomonas palustris on benzoate." Journal of bacteriology 177, no. 22 (1995): 6545–51. http://dx.doi.org/10.1128/jb.177.22.6545-6551.1995.

Full text
APA, Harvard, Vancouver, ISO, and other styles
10

Li, H., H. Xu, D. E. Graham, and R. H. White. "Glutathione synthetase homologs encode -L-glutamate ligases for methanogenic coenzyme F420 and tetrahydrosarcinapterin biosyntheses." Proceedings of the National Academy of Sciences 100, no. 17 (August 8, 2003): 9785–90. http://dx.doi.org/10.1073/pnas.1733391100.

Full text
APA, Harvard, Vancouver, ISO, and other styles
More sources

Dissertations / Theses on the topic "Coenzyme A Ligases"

1

Lelievre, Chloé. "Formation de liaisons amides par réactions enzymatiques détournées ATP Regeneration System in Chemoenzymatic Amide Bond Formation with Thermophilic CoA Ligase." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASF026.

Full text
Abstract:
La fonction amide est omniprésente dans les produits naturels et aussi dans de nombreux composés synthétiques comme des principes actifs et des polymères. De nombreuses approches ont été développées pour disposer de méthodes de synthèse efficaces. L'approche la plus courante en chimie conventionnelle est l'acylation d'une amine par un acide carboxylique activé. L'activation nécessite l'utilisation soit d'agents de couplage, résultant en une faible économie d'atomes, soit de catalyseurs couteux parfois utilisés dans des conditions drastiques. Les approches biocatalytiques sont donc des alternatives intéressantes pour des raisons économiques et environnementales. Différentes enzymes peuvent être utilisées comme des hydrolases, des nitrile hydratases et des transglutaminases qui activent l'acide sous forme acyl-enzyme pour favoriser l'addition nucléophile de l'amine. Depuis quelques années, l'intérêt pour les enzymes dépendantes de l'ATP s'est accru.Dans ce projet, nous nous sommes intéressés aux CoA ligases qui catalysent la formation d'acide activé sous forme d'acyl-adenylate puis acyl-thioester. Nous avons ainsi mis en évidence qu'en détournant la réaction par piégeage de l'intermédiaire activé par une amine, nous obtenons l'amide. L'utilisation de CoA ligases thermophiles permet de travailler à une température élevée et ainsi de faciliter l'addition non catalysée de l'amine. Ce système s'affranchit donc de l'utilisation de HSCoA onéreux. Pour un système efficace, nous avons aussi intégré avec succès un système de régénération de l'ATP comprenant une Polyphosphate Kinase 2 (Classe III) et une inorganique pyrophosphatase. L'efficacité de cette cascade a été illustrée par la synthèse chemo-enzymatique à l'échelle du laboratoire du N-méthylbutyrylamide avec un rendement de 77 % avec de faibles quantités en enzyme.L'exploration de la biodiversité par approche génomique basée sur la comparaison de séquence, nous a permis d'identifier plusieurs CoA ligases thermophiles actives sur des substrats ω-amino acides précurseurs de lactames. K6Q029 issue de Thermaerobacter subterraneus a fait l'objet d'études plus approfondies. Elle est notamment active sur des substrats ω-amino acides fonctionnalisés ou non, de chaines carbonées plus ou moins longues, mais aussi sur des acides carboxyliques variés tels que des aromatiques.Grâce à la résolution structurale d'A4YDT1, une CoA ligase promiscuitaire, nous avons identifié, en collaboration avec une équipe de cristallographes de l'université de Groningen (Pays Bas), les résidus impliqués dans sa spécificité de substrats pour les modifier par une approche rationnelle. Des mutants de cette enzyme ont ainsi permis l'obtention de δ-valerolactame et Ɛ-caprolactame
The amide function is widespread in nature and also in many synthetic products such as pharmaceuticals and polymers. Numerous approaches have been developed to provide reliable synthesis methods. The most common approach in conventional chemistry is the acylation of an amine by activated carboxylic acid. Activation requires the use of either coupling reagents resulting in low atom economy, or expensive catalysts sometimes used under drastic conditions. Biocatalytic approaches are therefore interesting alternatives for economic and environmental reasons. Different enzymes can be used such as hydrolases, nitrile hydratases and transglutaminases that activate the acid in acyl-enzyme form to promote the nucleophilic addition of the amine. In recent years, interest in ATP-dependent enzymes has increased.In this project, we focused on CoA ligases that catalyze the formation of activated acid as acyl-adenylate and then acyl-thioester. We have thus demonstrated that by diverting the reaction by scavenging activated intermediate with an amine, we obtain the amide. The use of thermophilic CoA ligases allows us to work at a high temperature and thus facilitate the uncatalyzed addition of the amine. This system therefore dispenses with the use of expensive HSCoA. For a better system, we have also successfully integrated an ATP regeneration system with a Polyphosphate Kinase 2 (Class III) and an inorganic pyrophosphatase. The efficiency of this cascade was illustrated by the lab-scale chemo-enzymatic synthesis of N-methylbutyrylamide in 77 % yield using low enzyme loading.Biodiversity exploration using a genomic approach based on sequence comparison allowed us to identify several thermophilic CoA ligases active towards ω-amino acid substrates. K6Q029 from Thermaerobacter subterraneus was further studied. In particular, this enzyme is active towards ω-amino acid substrates, functionalized or not, with more or less long carbon chains, as well as on various carboxylic acids such as aromatics.Thanks to the structural resolution of A4YDT1, a promiscuous CoA ligase from the literature, we have identified, in collaboration with a team of crystallographers from theUniversity of Groningen (Netherlands), the residues involved in its substrate specificity to modify them by a rational approach. Variants of this enzyme have thus allowed to obtain δ-valerolactam and Ɛ-caprolactam
APA, Harvard, Vancouver, ISO, and other styles
2

Styles, Nathan Allen. "The characterization of the subcellular localization of bile acid CoA:N-acyltransferase." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2007p/styles.pdf.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Quigley, Caitlin M. "The Drosophila Homolog of the Intellectual Disability Gene ACSL4 Acts in Glia to Regulate Morphology and Neuronal Activity: A Dissertation." eScholarship@UMMS, 2007. http://escholarship.umassmed.edu/gsbs_diss/839.

Full text
Abstract:
Recent developments in neurobiology make it clear that glia play fundamental and active roles, in the adult and in development. Many hereditary cognitive disorders have been linked to developmental defects, and in at least two cases, Rett Syndrome and Fragile X Mental Retardation, glia are important in pathogenesis. However, most studies of developmental disorders, in particular intellectual disability, focus on neuronal defects. An example is intellectual disability caused by mutations in ACSL4, a metabolic enzyme that conjugates long-chain fatty acids to Coenzyme A (CoA). Depleting ACSL4 in neurons is associated with defects in dendritic spines, a finding replicated in patient tissue, but the etiology of this disorder remains unclear. In a genetic screen to discover genes necessary for visual function, I identified the Drosophila homolog of ACSL4, Acsl, as a gene important for the magnitude of neuronal transmission, and found that it is required in glia. I determined that Acsl is required in a specific subtype of glia in the Drosophila optic lobe, and that depletion of Acsl from this population causes morphological defects. I demonstrated that Acsl is required in development, and that the phenotype can be rescued by human ACSL4. Finally, I discovered that ACSL4 is expressed in astrocytes in the mouse hippocampus. This study is highly significant for understanding glial biology and neurodevelopment. It provides information on the role of glia in development, substantiates a novel role for Acsl in glia, and advances our understanding of the potential role that glia play in the pathogenesis of intellectual disability.
APA, Harvard, Vancouver, ISO, and other styles
4

Quigley, Caitlin M. "The Drosophila Homolog of the Intellectual Disability Gene ACSL4 Acts in Glia to Regulate Morphology and Neuronal Activity: A Dissertation." eScholarship@UMMS, 2016. https://escholarship.umassmed.edu/gsbs_diss/839.

Full text
Abstract:
Recent developments in neurobiology make it clear that glia play fundamental and active roles, in the adult and in development. Many hereditary cognitive disorders have been linked to developmental defects, and in at least two cases, Rett Syndrome and Fragile X Mental Retardation, glia are important in pathogenesis. However, most studies of developmental disorders, in particular intellectual disability, focus on neuronal defects. An example is intellectual disability caused by mutations in ACSL4, a metabolic enzyme that conjugates long-chain fatty acids to Coenzyme A (CoA). Depleting ACSL4 in neurons is associated with defects in dendritic spines, a finding replicated in patient tissue, but the etiology of this disorder remains unclear. In a genetic screen to discover genes necessary for visual function, I identified the Drosophila homolog of ACSL4, Acsl, as a gene important for the magnitude of neuronal transmission, and found that it is required in glia. I determined that Acsl is required in a specific subtype of glia in the Drosophila optic lobe, and that depletion of Acsl from this population causes morphological defects. I demonstrated that Acsl is required in development, and that the phenotype can be rescued by human ACSL4. Finally, I discovered that ACSL4 is expressed in astrocytes in the mouse hippocampus. This study is highly significant for understanding glial biology and neurodevelopment. It provides information on the role of glia in development, substantiates a novel role for Acsl in glia, and advances our understanding of the potential role that glia play in the pathogenesis of intellectual disability.
APA, Harvard, Vancouver, ISO, and other styles
5

Bursby, Timothy Patrick. "Investigations of the mitochondrial #beta#-oxidation trifunctional protein and its association with complex 1 of the respiratory chain." Thesis, University of Newcastle Upon Tyne, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364807.

Full text
APA, Harvard, Vancouver, ISO, and other styles
6

Marty-Tommasi, Laurence. "Modélisation du centre actif de métalloprotéines à fer non hème. Complexes du fer avec des analogues de PQQ et des ligands à donneurs soufre et N-imidazole." Toulouse 3, 1995. http://www.theses.fr/1995TOU30022.

Full text
Abstract:
La premiere partie de ce travail concerne la synthese et l'etude des proprietes de quatre complexes du fer. Ils sont constitues d'analogues de synthese du pqq (pyrroloquinoleine quinone), dont deux sont sous forme reduite et un sous forme orthoquinonique. Les etudes par spectroscopie infrarouge, mossbauer et susceptibilite magnetique des quatre complexes, ont mis en evidence differentes nuclearites dependant de la stoechiometrie fe/l et du ph de la reaction. Trois sont caracterises par un rapport fe/2l (deux mononucleaires et un polynucleaire). Le quatrieme complexe dont la determination de la structure moleculaire a permis de mettre en evidence la forme dimere et le mode de coordination monodente pontant du carboxylate, est caracterise par un rapport fe/l. Le site de chelation privilegie des analogues de la forme reduite du pqq est constitue par l'azote pyridinique, la fonction acide adjacente a cet azote et l'oxygene methoxy ou hydroxy. Par contre le site de chelation privilegie de l'analogue de la forme oxydee fait intervenir les oxygenes quinoniques. La deuxieme partie de notre travail concerne la modelisation du centre actif des nitriles hydratases. Nous avons realise la synthese de quatre ligands bidentes renfermant simultanement des donneurs soufres et azotes. A partir de ces ligands, nous avons synthetise huit complexes du fer(ii) et etudie leurs proprietes spectrales (infrarouge, mossbauer) et magnetiques. Trois des quatre ligands conduisent a quatre complexes de stoechiometrie 2l/fe alors que le ligand 1h-benzimidazole-2-ethanethiol donne des complexes de stoechiometrie 3l/2fe: fe#i#i#2(lh)#3, x, ymeoh avec x = acetate, perchlorate ou chlorure, y = 1 ou 1,5. Le complexe fe#i#i(lh)#2, h#2o qui renferme deux ligands benzenethiol,2-(1h-benzimidazole-2-yl), lh#2 possede des caracteristiques (environnement de ligands de type n#2os#2) compatibles avec la modelisation du site actif des nitrile hydratases
APA, Harvard, Vancouver, ISO, and other styles
7

Ramkumar, Charusheila. "Antagonistic Pleiotropy: The Role of Smurf2 in Cancer and Aging: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/634.

Full text
Abstract:
In response to telomere shortening, oxidative stress, DNA damage or aberrant activation of oncogenes, normal somatic cells exit the cell cycle and enter an irreversible growth arrest termed senescence. The limited proliferative capacity imposed by senescence on cells impedes the accumulation of mutations necessary for tumorigenesis and prevents proliferation of cells at risk of neoplastic transformation. Opposite to the tumor suppressor function, accumulation of senescent cells in adult organisms is thought to contribute to aging by depleting the renewal capacity of tissues and stem/progenitor cells, and by interfering with tissue homeostasis and functions. The Antagonistic Pleiotropy Theory of senescence proposes that senescence is beneficial early in life by acting as a tumor suppressor, but harmful late in life by contributing to aging. Recent studies have provided evidence strongly supporting the tumor suppressor function of senescence, however, direct evidence supporting the role of senescence in aging remains largely elusive. In this thesis, I describe studies to test the Antagonistic Pleiotropy Theory of senescence in tumorigenesis and aging. The approach that I have taken is to alter the senescence response in vivo by changing the expression of a senescence regulator in mice. The consequence of altered senescence response on tumorigenesis and stem cell self-renewal was investigated. The senescence regulator I studied is Smurf2, which has been shown previously to activate senescence in culture. I hypothesized that the senescence response will be impaired by Smurf2 deficiency in vivo. Consequently, Smurf2-deficient mice will develop tumors at an increased frequency, but also gain enhanced self-renewal capacity of stem/progenitor cells with age. I generated a Smurf2-deficient mouse model, and found that Smurf2 deficiency attenuated p16 expression and impaired the senescence response in primary cells and tissues. Smurf2-deficient mice exhibited an increased susceptibility to spontaneous tumorigenesis, indicating that Smurf2 is a tumor suppressor. At the premalignant stage of tumorigenesis, a defective senescence response was documented in the Smurf2-deficient mice, providing a mechanistic link between impaired senescence response and increased tumorigenesis. The majority of tumors developed in Smurf2-deficent mice were B-cell lymphomas with an origin in germinal centers of the spleen and a phenotype resembling human diffuse large B-cell lymphoma (DLBCL). I discovered that Smurf2 mediated ubiquitination of YY1, a master regulator of germinal centers. Stabilization of YY1 in the absence of Smurf2 was responsible for increased cell proliferation and drove lymphomagenesis in Smurf2-deficient mice. Consistently, a significant decrease of Smurf2 expression was observed in human primary DLBCL samples, and more importantly, a low level of Smurf2 expression in DLBCL correlated with poor survival prognosis. Moreover, I found that hematopoietic stem cells (HSCs) in Smurf2-deficient mice had enhanced function compared to wild-type controls. This enhanced stem cell function was associated with increased cell proliferation and decreased p16 expression, suggesting that defective senescence response in Smurf2-deficient mice leads to increased self-renewal capacity of HSCs. My study, for the first time, offers direct genetic evidence of an important tumor suppressor function for Smurf2 as well as its function in contributing to stem cell aging. Collectively, these findings provide strong evidence supporting the Antagonistic Pleiotropy Theory of senescence in tumorigenesis and aging.
APA, Harvard, Vancouver, ISO, and other styles
8

Weiss, Eric R. "Investigating the Roles of NEDD4.2s and Nef in the Release and Replication of HIV-1: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/641.

Full text
Abstract:
Replication of HIV-1 requires the assembly and release of mature and infectious viral particles. In order to accomplish this goal, HIV-1 has evolved multiple methods to interact with the host cell. HIV-1 recruits the host cell ESCRT machinery to facilitate the release of nascent viral particles from the host cell membrane. Recruitment of these cellular factors is dependent on the presence of short motifs in Gag referred to as Late-domains. Deletion or mutation of these domains results in substantial decrease in the release of infectious virions. However, previously published work has indicated that over-expression of the E3 ubiquitin ligase, NEDD4.2s is able to robustly rescue release of otherwise budding-defective HIV-1 particles. This rescue is specific to the NEDD4.2s isoform as related E3 ubiquitin ligases display no ability to rescue particle release. In addition, rescue of particle release is dependent on the presence of the partial C2 domain and a catalytically active HECT domain of NEDD4.2s. Here I provide evidence supporting the hypothesis that a partial C2 domain of NEDD4.2s constitutes a Gag interacting module capable of targeting the HECT domains of other E3 ubiquitin ligases to HIV-1 Gag. Also, by generating chimeras between HECT domains shown to form poly-ubiquitin chains linked through either K48 or K63 of ubiquitin, I demonstrate that the ability of NEDD4.2s to catalyze the formation of K63-polyubiquitin chains is required for its stimulation of HIV-1 L-domain mutant particle release. In addition, I present findings from on-going research into the role of the HIV-1 accessory protein Nef during viral replication using the culture T-cell line, MOLT3. My current findings indicate that downregulation of CD4 from the host cell membrane does not solely account for the dramatic dependence of HIV-1 replication on Nef expression in this system. In addition, I present evidence indicating that Nef proteins from diverse HIV-1 Groups and strains are capable of enhancing HIV-1 replication in this system. Analysis of a range of mutations in Nef known to impact interaction with cellular proteins suggest that the observed replication enhancement requires Nef targeting to the host cell membrane and may also require the ability to interact with select Src-kinases. Lastly, we find that the ability of Nef to enhance replication in this system is separate from any increase in viral particle infectivity, in agreement with current literature.
APA, Harvard, Vancouver, ISO, and other styles
9

Ramadan, Hussein [Verfasser]. "Molecular analysis of coenzyme A ligase from benzoate-metabolizing Sorbus aucuparia cell cultures / von Hussein Ramadan." 2006. http://d-nb.info/983473323/34.

Full text
APA, Harvard, Vancouver, ISO, and other styles

Book chapters on the topic "Coenzyme A Ligases"

1

Schomburg, Dietmar, and Ida Schomburg. "coenzyme F420-0:l-glutamate ligase 6.3.2.31." In Class 3.4–6 Hydrolases, Lyases, Isomerases, Ligases, 674–77. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-36260-6_89.

Full text
APA, Harvard, Vancouver, ISO, and other styles
2

Schomburg, Dietmar, and Ida Schomburg. "coenzyme F420-1:γ-l-glutamate ligase 6.3.2.34." In Class 3.4–6 Hydrolases, Lyases, Isomerases, Ligases, 683–86. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-36260-6_92.

Full text
APA, Harvard, Vancouver, ISO, and other styles
3

Schomburg, Dietmar, and Ida Schomburg. "coenzyme γ-F420-2:α-l-glutamate ligase 6.3.2.32." In Class 3.4–6 Hydrolases, Lyases, Isomerases, Ligases, 678–80. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/978-3-642-36260-6_90.

Full text
APA, Harvard, Vancouver, ISO, and other styles
4

"6.6 Coenzyme der Lyasen, Isomerasen und Ligasen." In Taschenlehrbuch Biologie Biochemie · Zellbiologie, edited by Katharina Munk. Stuttgart: Georg Thieme Verlag, 2008. http://dx.doi.org/10.1055/b-0034-29173.

Full text
APA, Harvard, Vancouver, ISO, and other styles
You might also be interested in the extended bibliographies on the topic 'Coenzyme A Ligases' for particular source types:
Journal articles
We offer discounts on all premium plans for authors whose works are included in thematic literature selections. Contact us to get a unique promo code!

To the bibliography