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Dissertationen zum Thema „Sequence-Structure relationship“

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1

Wang, Pam Shou-Ping. „Exploring the sequence-structure-function relationship in beta-peptide foldamers“. Thesis, Yale University, 2014. http://pqdtopen.proquest.com/#viewpdf?dispub=3580893.

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The interplay between sequence, structure and function is an underlying theme in biological systems. Proteins, in particular, have evolved the ability to access a virtually infinite set of three-dimensional architectures from a small collection of building blocks; it is precisely this complexity of form that finely tunes their functional specificity. β-Peptides are a class of unnatural polyamides known to adopt structural motifs that are in many ways reminiscent of protein folds in nature. This dissertation first investigates the relationship between sequence and structure in self-assembling β-peptides, then demonstrates how the latter translates into function.

Chapter 1 provides an overview of the fundamental principles guiding β-peptide helix formation and self-assembly, and describes their applications both within and outside of the biological context. The ability of β-peptides to mimic natural α-helices while maintaining proteolytic resistance allows them to serve as therapeutic agents by targeting, for example, protein-protein interactions. Their unique stability in both aqueous and organic environments further enables the development of β-peptide-based nanomaterials and organocatalysts.

Chapter 2 elucidates the relationship between β-peptide primary sequence and quaternary structure based on the biophysical characterization of the Acid-3Y bundle. Acid-3Y was designed by substituting isoleucine for leucine side-chains in the sequence of the previously characterized octamer, Acid-1Y. The finding that Acid-3Y assembles into a tetrameric bundle suggests that branching at the γ-carbon of hydrophobic residues plays a critical role in determining β-peptide bundle stoichiometry.

Chapter 3 explores the potential of β-peptide bundles to mimic enzyme structure and function. The demonstration of β-peptide mutarotase activity in benzene highlights the importance of macromolecular preorganization in catalysis, while the ability of rationally designed β-peptide bundles to catalyze ester hydrolysis in water represents a crucial step towards the functionalization of these unnatural macromolecules. The dependence of catalytic activity on both active site geometry and bundle assembly, together with their substrate selectivity, underscores the unique biomimetic capacity of β-peptides.

Chapter 4 describes the rational design of a β-peptide ligand for the parathyroid hormone 1 receptor (PTH1R). Using previous strategies that led to the identification of p53 and GLP-1 mimics, a 12-member β-peptide library was constructed and tested in vitro for binding to the receptor protein. Although no hits were found from this initial screen, subsequently designed α/β-peptide chimeras showed promise as synthetic antagonists of PTH1R with improved pharmacokinetic properties.

Chapter 5 summarizes the key results of this dissertation and offers a perspective on possible future research directions. A breakthrough in the field of β-peptides would rely on the development of a method to synthesize genuine "β-proteins" with more sophisticated structure and function.

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2

Mokrab, Younes. „Insights into sequence-structure relationship in helical transmembrane proteins : application to comparative modeling“. Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611915.

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3

Viklund, Håkan. „Formalizing life : Towards an improved understanding of the sequence-structure relationship in alpha-helical transmembrane proteins“. Doctoral thesis, Stockholm University, Department of Biochemistry and Biophysics, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7144.

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Genes coding for alpha-helical transmembrane proteins constitute roughly 25% of the total number of genes in a typical organism. As these proteins are vital parts of many biological processes, an improved understanding of them is important for achieving a better understanding of the mechanisms that constitute life.

All proteins consist of an amino acid sequence that fold into a three-dimensional structure in order to perform its biological function. The work presented in this thesis is directed towards improving the understanding of the relationship between sequence and structure for alpha-helical transmembrane proteins. Specifically, five original methods for predicting the topology of alpha-helical transmembrane proteins have been developed: PRO-TMHMM, PRODIV-TMHMM, OCTOPUS, Toppred III and SCAMPI.

A general conclusion from these studies is that approaches that use multiple sequence information achive the best prediction accuracy. Further, the properties of reentrant regions have been studied, both with respect to sequence and structure. One result of this study is an improved definition of the topological grammar of transmembrane proteins, which is used in OCTOPUS and shown to further improve topology prediction. Finally, Z-coordinates, an alternative system for representation of topological information for transmembrane proteins that is based on distance to the membrane center has been introduced, and a method for predicting Z-coordinates from amino acid sequence, Z-PRED, has been developed.

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4

Viklund, Håkan. „Formalizing life : towards an improved understanding of the sequence-structure relationship in alpha-helical transmembrane proteins /“. Stockholm : Department of Biochemistry and Biophysics, Stockholm University, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-7144.

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5

Zheng, Ying. „Functional divergence after gene duplication and sequence-structure relationship a case-study of G-protein alpha subunits /“. [Ames, Iowa : Iowa State University], 2007.

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6

Shafqat, Naeem. „Substrate specificities and functional properties of human short-chain dehydrogenases/reductases /“. Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-829-7.

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7

Chevallier, Sylvie. „Relations structure-fonction de l'oligopeptidase proline-spécifique (EC 3. 4. 21. 26) de Flavobacterium meningosepticum“. Grenoble 1, 1993. http://www.theses.fr/1993GRE10076.

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L'oligopeptidase proline-specifique (pop) de f. Meningosepticum coupe presque exclusivement du cote c-terminal des prolines et des hydroxyprolines. Le remplacement d'une proline par un acide pipecolique transforme un substrat en un inhibiteur, ce qui confirme la forte stereospecificite de la pop au niveau du sous-site s1. La sequence proteique a ete determinee par sequencage chimique de la pop, et clonage et sequencage de son gene (2115 pb). La pop mature periplasmique comporte 685 residus pour une masse moleculaire de 76784 da et montre des homologies de sequence uniquement avec la pop de cerveau de porc (38%) et la protease ii d'e. Coli (24%). La sequence grsng comprenant la serine 536 du site actif marquee par le diisopropylfluorophosphate tritie est distincte de celle du site actif des proteases a serine connues, bien qu'elle soit en correlation avec la sequence consensus gxsxg/a. Les residus presumes de la triade catalytique de la pop (s536, d621, h655) sont disposes dans un ordre different de ceux de la chymotrypsine (h57, d102, s195) et de la subtilisine (d32, h64, s221), mais similaire a celui de la carboxypeptidase y (s146, d338, h397). L'existence de trois domaines n-terminaux structuralement analogues a l'immunophiline humaine fkbp-12 et d'un domaine catalytique c-terminal de structure alpha-beta hydrolase fold a ete demontree par analyse hca de la pop. Les pops et la protease ii d'e. Coli forment donc une nouvelle famille de proteases a serine structuralement proches de la dienelactone hydrolase et de la carboxypeptidase ii dont les domaines catalytiques montrent un repliement de type alpha-beta hydrolase
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8

Vignoud, Lucile. „Étude du rôle des motifs NPXY dans la fonction de l'intégrine alpha 5/beta 1“. Grenoble 1, 1996. http://www.theses.fr/1996GRE10274.

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Le travail presente concerne l'etude du role joue par les deux motifs peptidiques npxy localises dans le domaine cytoplasmique de la sous-unite beta 1 des integrines. Par analogie avec le recepteur des ldl, ces deux motifs etaient assimiles au signal d'internalisation npxy permettant une association au complexe d'adaptines ha-2 et une internalisation dependante des puits a clathrine. En generant des lignees stables exprimant des integrines a sous-unite beta 1 mutees, nous avons montre que contrairement a d'autres recepteurs, les motifs npxy n'intervenaient pas dans l'internalisation de l'integrine alpha 5/beta 1. En revanche, nous avons observe que chacun des motifs npxy etait indispensable a l'assemblage des adherences focales. L'affinite pour le ligand extracellulaire n'etant pas affectee par les mutations realisees, nos resultats attribuent aux deux motifs npxy un role en tant que sites d'interaction, ou permettant la formation de sites d'interaction, avec une ou plusieurs proteines cytoplasmiques necessaires a l'assemblage des adherences focales. L'analyse de la fixation in vitro de la taline sur les chaines beta 1 mutees au niveau des sequences npxy, indique que cette proteine, pourtant necessaire a l'etablissement des adherences focales, n'est pas la proteine cible qui interagit avec les motifs npxy des integrines pour permettre leur recrutement au sein de ces adherences. La taline n'est pas suffisante a elle seule pour permettre l'assemblage des adherences focales. L'identite des proteines interagissant avec la sous-unite beta 1 de maniere dependante des motifs npxy, reste a determiner. L'immunoprecipitation des integrines a sous-unite beta 1 humaine dans des conditions menagees, a mis en evidence leur association avec diverses proteines cellulaires, controlee par le premier motif npxy (tyr 783). Ces proteines, non identifiees, pourraient jouer un role essentiel dans l'organisation des adherences focales, dependante du premier motif npxy de la sous-unite beta 1 des integrines, et/ou dans la signalisation cellulaire
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9

Lombard, Valentin. „Geometric deep manifold learning combined with natural language processing for protein movies“. Electronic Thesis or Diss., Sorbonne université, 2024. http://www.theses.fr/2024SORUS379.

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Les protéines jouent un rôle central dans les processus biologiques, et comprendre comment elles se déforment et se déplacent est essentiel pour élucider leurs mécanismes fonctionnels. Malgré les récentes avancées dans les technologies à haut débit, qui ont élargi nos connaissances sur les structures protéiques, la prédiction précise de leurs différents états conformationnels et mouvements reste un défi majeur. Nous présentons deux approches complémentaires pour relever le défi de la compréhension et de la prédiction de l'ensemble de la variabilité conformationnelle des protéines. La première approche, appelée Dimensionality Analysis for protein Conformational Exploration (DANCE), permet une description systématique et complète de la variabilité conformationnelle des familles de protéines. DANCE prend en compte à la fois les structures expérimentales et prédites. Elle est adaptée à l'analyse des protéines individuelles jusqu'aux superfamilles. En l'utilisant, nous avons regroupé toutes les structures protéiques résolues expérimentalement disponibles dans la banque de données Protein Data Bank en collections conformationnelles et les avons caractérisées comme des ensembles de mouvements linéaires. Cette ressource facilite l'accès et l'exploitation des multiples états adoptés par une protéine et ses homologues. Au-delà de l'analyse descriptive, nous avons évalué des techniques classiques de réduction de la dimensionnalité pour échantillonner des états non observés sur un banc d'essai représentatif. Ce travail améliore notre compréhension de la manière dont les protéines se déforment pour accomplir leurs fonctions et ouvre la voie à une évaluation standardisée des méthodes conçues pour échantillonner et générer des conformations protéiques. La deuxième approche repose sur l'apprentissage profond pour prédire des représentations continues du mouvement des protéines directement à partir de séquences, sans avoir besoin de données structurelles. Ce modèle, appelé SeaMoon, utilise des embeddings de modèles de langage protéique (pLM) comme entrées dans un réseau neuronal convolutif léger comptant environ un million de paramètres entraînables. SeaMoon atteint un taux de réussite de 40 % lorsqu'il est évalué sur environ 1 000 collections de conformations expérimentales, capturant des mouvements au-delà de la portée des méthodes traditionnelles comme l'analyse des modes normaux, qui repose uniquement sur la géométrie 3D. De plus, SeaMoon se généralise à des protéines n'ayant aucune similitude de séquence détectable avec son ensemble d'entraînement et peut être facilement réentraîné avec des pLM mis à jour. Ces deux approches offrent un cadre unifié pour faire progresser notre compréhension de la dynamique des protéines. DANCE fournit une exploration détaillée des mouvements protéiques basée sur des données structurelles, tandis que SeaMoon démontre le potentiel des modèles d'apprentissage profond basés sur les séquences pour capturer des mouvements complexes sans dépendre d'informations structurelles explicites. Ensemble, elles ouvrent la voie à une compréhension plus complète de la variabilité conformationnelle des protéines et de son rôle dans la fonction biologique
Proteins play a central role in biological processes, and understanding how they deform and move is essential to elucidating their functional mechanisms. Despite recent advances in high-throughput technologies, which have broadened our knowledge of protein structures, accurate prediction of their various conformational states and motions remains a major challenge. We present two complementary approaches to address the challenge of understanding and predicting the full range of protein conformational variability. The first approach, Dimensionality Analysis for protein Conformational Exploration (DANCE) for a systematic and comprehensive description of protein families conformational variability. DANCE accommodates both experimental and predicted structures. It is suitable for analyzing anything from single proteins to superfamilies. Employing it, we clustered all experimentally resolved protein structures available in the Protein Data Bank into conformational collections and characterized them as sets of linear motions. The resource facilitates access and exploitation of the multiple states adopted by a protein and its homologs. Beyond descriptive analysis, we assessed classical dimensionality reduction techniques for sampling unseen states on a representative benchmark. This work improves our understanding of how proteins deform to perform their functions and opens ways to a standardized evaluation of methods designed to sample and generate protein conformations. The second approach relies on deep learning to predict continuous representations of protein motion directly from sequences, without the need for structural data. This model, SeaMoon, uses protein language model (pLM) embeddings as inputs to a lightweight convolutional neural network with around 1 million trainable parameters. SeaMoon achieves a success rate of 40% when evaluated against around 1,000 collections of experimental conformations, capturing movements beyond the reach of traditional methods such as normal mode analysis, which relies solely on 3D geometry. In addition, SeaMoon generalizes to proteins that have no detectable sequence similarity with its training set and can be easily retrained with updated pLMs. These two approaches offer a unified framework for advancing our understanding of protein dynamics. DANCE provides a detailed exploration of protein movements based on structural data, while SeaMoon demonstrates the potential of sequence-based deep learning models to capture complex movements without relying on explicit structural information. Together, they pave the way for a more comprehensive understanding of protein conformational variability and its role in biological function
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10

Pauly, Marc. „Etude structurale et fonctionnelle de la sequence tata du promoteur precoce du virus simien sv40“. Université Louis Pasteur (Strasbourg) (1971-2008), 1989. http://www.theses.fr/1989STR13043.

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Dans le but d'elucider les mecanismes moleculaires de la regulation de l'expression des genes, une etude structurale et fonctionnelle detaillee de la sequence tata du promoteur precoce du virus sv40 est realisee. La mutagenese dirigee utilisant des oligodesoxynucleotides de synthese permet la localisation des domaines fonctionnels de deux elements tata situes dans la region d'origine de replication virale. Chacun des elements dirige independamment l'initiation precise et efficace de la transcription precoce in vivo a partir d'un groupe de sites definis
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11

Naud, Isabelle. „Caractérisation fonctionnelle de la ferrédoxine I de Rhodobacter capsulatus : identification et caractérisation d'une sixième ferrédoxine“. Université Joseph Fourier (Grenoble), 1994. http://www.theses.fr/1994GRE10063.

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La ferredoxine 1 (fd1) de rhodobacter capsulatus est une ferredoxine a deux centres 4fe-4s. On la considere comme le transporteur physiologique d'electrons a la nitrogenase. Pour caracteriser fonctionnellement fd1, nous avons etudie un mutant fd1- dans lequel son gene fdxn est inactive par insertion d'un interposon: fd1 n'est pas essentielle a la fixation d'azote. L'activite nitrogenase est dix a vingt fois inferieure a celle du parent sauvage ; les deux composants de la nitrogenase sont quatre a cinq fois moins synthetises. Le gene fdxn reintroduit permet une complementation totale en trans de la souche fd1-. Par ailleurs, la souche fd1- produit deux a trois fois plus de ferredoxine 5. Par mutagenese dirigee, trois genes mutants du gene fdxn ont ete generes. Ils ont ete exprimes dans escherichia coli et dans la souche fd1- de rhodobacter capsulatus. Dans ce dernier cas, le systeme d'expression a permis d'analyser in vivo la competence des proteines mutantes. Celles-ci se sont revelees peu differentes de fd1 sauvage. Apres purification, nous avons caracterise les ferredoxines mutantes: l'environnement de leurs centres 4fe-4s n'est quasiment pas modifie. Leur capacite d'interaction in vitro avec la nitrogenase a ete mesuree par des tests enzymatiques et des pontages chimiques. L'aspartate 36 de fd1 jouerait un role crucial dans la reconnaissance entre les deux partenaires redox. Un modele tridimensionnel de fd1 a ete elabore par modelisation graphique. Au cours de la purification des fd1 mutantes, une nouvelle ferredoxine a ete isolee de rhodobacter capsulatus (fd6). Elle est constituee de 106 acides amines et contient un centre 2fe-2s. Elle est tres proche de la ferredoxine de caulobacter crescentus et de la putidaredoxine de pseudomonas putida ; sa synthese ne semble pas regulee par le substrat azote
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12

Williams, Amy. „Studies of sequence structure relationships in distantly related proteins“. Thesis, University of Leeds, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.396928.

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13

Guy, Philippe. „Utilisation de la spectrométrie de masse pour l'étude structurale des protéines“. Université Joseph Fourier (Grenoble), 1996. http://www.theses.fr/1996GRE10085.

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Nous decrivons les progres recents de la spectrometrie de masse dans l'etude structurale des proteines. Nos etudes associent la degradation chimique d'edman, les hydrolyses enzymatiques et les analyses par esims pour resoudre des problemes specifiques a la caracterisation de la structure primaire des proteines. Ainsi nous montrons qu'il est possible de preparer des sels d'ammonium quaternaires d'isothiocyanates par synthese chimique et de les utiliser dans les conditions de la degradation d'edman. La detection des produits resultants est realisee par esims afin d'ameliorer la sensibilite et d'assurer la caracterisation de certains residus. La connaissance de la structure primaire des proteines nous a conduit a l'etude de la localisation des ponts disulfures, responsables en partie du maintien de la structure tridimensionnelle des proteines. Une approche nouvelle utilisant la tris-(2-carboxyethyl) phosphine pour la reduction des ponts disulfures et le n-hydroxymethyl benzamide comme methode d'alkylation des cysteines libres en milieu acide est presentee. Apres avoir realise une etude comparative de peptides lies a l'aide d'un pont disulfure par sm avec divers modes d'ionisation, nous avons identifie ceux des puroindolines a et b de ble. Enfin, par esims, nous avons obtenu des renseignements sur la stabilite et la conformation des cytochromes c#2 et c#5#5#3 sauvages et mutes. Nous avons mis en evidence la presence de plusieurs conformeres de proteines par observation de la distribution des etats de charges et par la mesure des echanges isotopiques (h/d). Nous avons ainsi classe en fonction de leur stabilite, les mutants des deux cytochromes par rapport aux types sauvages. De plus, nous avons mis au point et realise l'etude des sites de deuteriation des hydrogenes amidiques du squelette polypeptidique. Celle-ci utilise les echanges isotopiques suivis d'une digestion rapide par la pepsine permettant d'obtenir des informations locales sur la penetration du solvant deuterie dans la proteine
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14

Kinahan, Michelle Elizabeth. „Tunable silk: using microfluidics to investigate sequence-structure-property relationships“. Thesis, Boston University, 2013. https://hdl.handle.net/2144/12794.

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Thesis (Ph.D.)--Boston University PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.
Silk is an ancient material that is produced in nature by both silkworms and spiders and has been used in textiles for thousands o·f years. Stronger than steel and tougher than Kevlar, silk fibers possess a unique combination of strength and elasticity. Silk is also biodegradable and biocompatible, and has been the focus of research areas ranging from fiber optics to tissue regeneration. While textile applications utilize raw silkworm silk, biomedical applications rely primarily on regenerated silk, which is derived from silkworm cocoons and reprocessed into the desired material. Additionally, there has been much progress in the area of recombinant silk technology, where genetically engineered proteins are inspired by or mimic: native silk sequences. However, despite major advancements in silk engineering, native silk spinning - a remarkable process that takes place at ambient temperature and pressure- is still not completely understood. Given these gaps in knowledge, it remains a challenge in the field to fabricate a regenerated or recombinant material that can mimic the outstanding properties of native silks. We have developed a novel microfluidic silk processing technique that mimics aspects of silkworm spinning to transform aqueous silk solution into fibers in a highly controlled manner. By altering flow parameters within the device and utilizing post-spin processing, we can tune properties such as fiber diameter and Young's modulus across a broad range for tailored applications. Unlike alternative processing methods, we can fabricate a fiber from as little as 50 micro-liters of silk solution or spin continuously for up to two hours to produce a non-woven mesh from a single fiber approximately 6.5 meters long. Using this device we have fabricated regenerated silk fibers to investigate cell behavior, incorporated silk fibers into cell sheets to provide structural support, and fabricated non-woven silk meshes for use as structural support layers for multi-layer tissue constructs. We have also spun multiple variants of recombinant silk-like sequences. We have optimized this device for use as a low-volume sequence screening tool as part of a combined computational and experimental approach to further the understanding of both native and recombinant silk protein folding and hierarchical assembly.
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Berti, Paul J. (Paul Joseph). „Cysteine proteases : interaction with cystatin C and sequence to structure-function relationships“. Thesis, McGill University, 1993. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=41350.

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An alignment/phylogeny of the papain superfamily of cysteine proteases was created from which the existence of at least 11 families of mammalian cysteine proteases was inferred, including two as yet uncharacterized ones. Character weighting increased the average speed of maximum parsimony phylogenetic searches two- to three-fold. To study a sequence motif in pro-cysteine proteases and mammalian cystatins, cystatin C, a cysteine protease inhibitor, was expressed and purified using a new affinity method giving $>$99% purity. Methionine oxidation to the sulfoxide occurring during protein production was eliminated. Reduced stability caused by Met14 oxidation was demonstrated. No function for the sequence motif was found, however cystatin C underwent a conformational change at acidic pH that rendered the His86-Asp87 peptide bond labile to proteolysis. This could constitute a mechanism for clearing inappropriately localized cystatins from the acid environment of lysosomes and explain differences between the X-ray and NMR structures of the homologous chicken cystatin.
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16

Simms, Amy Nicole. „Examination of Neisseria gonorrhoeae opacity protein expression during experimental murine genital tract infection /“. Download the dissertation in PDF, 2005. http://www.lrc.usuhs.mil/dissertations/pdf/Simms2005.pdf.

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17

Steffen-Munsberg, Fabian [Verfasser]. „Structure– and sequence–function relationships in (S)-amine transaminases and related enzymes / Fabian Steffen-Munsberg“. Greifswald : Universitätsbibliothek Greifswald, 2015. http://d-nb.info/1074259610/34.

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18

Chursov, Andrey [Verfasser], Dimitri [Akademischer Betreuer] Frischmann und Burkhard [Akademischer Betreuer] Rost. „Sequence-structure relationships in mRNAs / Andrey Chursov. Gutachter: Dimitri Frischmann ; Burkhard Rost. Betreuer: Dimitri Frischmann“. München : Universitätsbibliothek der TU München, 2013. http://d-nb.info/1047678918/34.

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19

Soares, Dinesh Christopher. „Bioinformatics studies on sequence, structure and functional relationships of proteins involved in the complement system“. Thesis, University of Edinburgh, 2007. http://hdl.handle.net/1842/11424.

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Regulators of complement activation (RCA) ensure that a complement-mediated immune response is proportionate and targeted against infection. RCA proteins are characterised by numerous occurrences of a single module-type; the complement control protein (CCP) module. In this work, comprehensive bioinformatics analyses of sequence and structure of CCP modules was undertaken. Through extensive database and literature searches, CCP module sequences and structures were assembled and large-scale all-against-all sequence and structure comparisons performed, along with analysis of intermodular orientations for pairs of modules and larger fragments. Based upon optimal use of experimentally determined CCP module structures as templates, an automated large-scale protein structure comparative modelling procedure was implemented for a large set of CCP-module sequences. The models are publicly available online at “The CCP module model database”, which also serves as a comprehensive resource for information on CCP modules. The models are shown to serve as a rich vein of information for design of mutants, interpretation of phenotypic consequences of polymorphisms, and prediction of function. For example, the models proved useful for inferring the consequences of several disease-associated sequence variations of complement proteins, CR1, factor H, MCP; and another CCP-containing protein, SRPX2. Finally, homology models of C5 and C5b were created on the basis of the recent landmark publication of C3 and C3b structures. This exercise revealed the existence of a novel putative disulfide bond specific to C5. Additionally it helped revisit previous peptide and mutant-based studies and provided insight into the latter stages of complement assembly.
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20

Vogel, Constantin [Verfasser], und Jürgen [Akademischer Betreuer] Pleiss. „Systematic analysis of the sequence-structure-function relationships of thiamine diphosphate-dependent enzymes / Constantin Vogel. Betreuer: Jürgen Pleiss“. Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2015. http://d-nb.info/1069815462/34.

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21

Dal, Maso Fabrice. „Influence du vieillissement thermique sur la morphologie et les proprietes du poly(fluorure de vinylidene) (pvf#2)“. Paris 6, 1992. http://www.theses.fr/1992PA066104.

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L'objet de la these est de decrire et de correler les evolutions de la morphologie et des proprietes du poly(fluorure de vinylidene) (pvf#2) au cours du vieillissement thermique, en fonction des conditions de mise en forme, de la temperature et de la duree de recuit. Contrairement a la plupart des etudes sur le pvf#2, les echantillons utilises sont obtenus par compression sous forme de plaques epaisses de plusieurs millimetres. Le mode de refroidissement est le parametre de moulage qui influence le plus le comportement a long terme du materiau. Du point de vue mecanique, le materiau conserve de bonnes proprietes et se stabilise apres quelques jours de recuit. Un aspect etonnant de ce materiau est que sa ductilite augmente, bien que sa cristallinite augmente egalement. La micro-structure du materiau est un arrangement complexe d'unites cristallines et amorphes, qui peuvent etre considerees a plusieurs echelles. La description de la micro-structure a donc necessite l'emploi de plusieurs techniques de caracterisation physico-chimiques (calorimetrie, diffraction des rayons x, microscopie, etc. ). La structure cristalline preferentiellement adoptee est la phase alpha. Le vieillissement n'entraine pas de transitions allotropiques. Par contre, l'organisation des zones cristallines est complexe et on observe des evolutions au niveau de la conformation des chaines, des empilements des chaines dans le cristal et de l'organisation des micro-domaines cristallins. C'est grace a la simulation des spectres des rayons x aux grands angles qu'il a ete possible de comprendre les evolutions des zones cristallines au cours du recuit. Une seconde approche, originale, a consiste a coupler un module de simulation de spherolites avec une simulation de diffraction des rayons x aux petits angles. Ces deux methodes de simulation informatique nous ont permis d'ameliorer la description de la structure du pvf#2 et d'autres polymeres semi-cristallins
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22

Buchholz, Patrick Christopher Frank [Verfasser], und Jürgen [Akademischer Betreuer] Pleiss. „Data integration and data mining for the exploration of enzymatic sequence-structure-function relationships / Patrick Christopher Frank Buchholz ; Betreuer: Jürgen Pleiss“. Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2018. http://d-nb.info/1173163808/34.

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23

Buchholz, Patrick C. F. [Verfasser], und Jürgen [Akademischer Betreuer] Pleiss. „Data integration and data mining for the exploration of enzymatic sequence-structure-function relationships / Patrick Christopher Frank Buchholz ; Betreuer: Jürgen Pleiss“. Stuttgart : Universitätsbibliothek der Universität Stuttgart, 2018. http://d-nb.info/1173163808/34.

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24

Roma, Glenn W. „Systematic Analysis of Structure-Function Relationships of Conserved Sequence Motifs in the NADH-Binding Lobe of Cytochrome b5 Reductase“. [Tampa, Fla] : University of South Florida, 2008. http://purl.fcla.edu/usf/dc/et/SFE0002558.

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25

Lu, Chih-Hao, und 陸志豪. „On the sequence-structure-dynamics relationship of proteins“. Thesis, 2007. http://ndltd.ncl.edu.tw/handle/65567716356118936976.

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博士
國立交通大學
生物資訊研究所
96
Disulfide bonds play important roles in both stabilizing the protein conformations and regulating protein functions. The ability to infer disulfide connectivity directly from protein sequences will be useful in structural modeling and in functional analysis. However, the prediction of disulfide connectivity from protein sequences presents a major challenge to computational biologists due to the nonlocal nature of disulfide connectivity, i.e., close spatial proximity of the cysteine pair that forms a disulfide bond does not necessarily imply short sequence separation between the cysteines. Recently, Chen and Hwang have developed an approach with each distinct disulfide pattern defined as a class, and treat the problem as a multi-class classification using the support vector machine technique. Their method significantly improves the prediction accuracy of disulfide connectivity for a standard benchmark dataset sharing less than 30% sequence identity. However, this method suffers from the drawback that the number of possible disulfide patterns grows rapidly when disulfide bonds increase. The performance of the method quickly drops off as the number of disulfide bonds increases. In this work, we represent the disulfide patterns in terms of cysteine pairs. We predict the bonding states of the cysteine pairs using support vector machine together with feature selection through the genetic algorithm. Since the number of bonding states of the cysteine pairs remains constant independent of the number of disulfide bonds, we avoid the problem of class explosion upon larger number of disulfide bonds. Consequently, we construct the connectivity matrix from the bonding states of the cysteine pairs to predict the complete disulfide pattern. Our approach outperforms other current approaches and may provide a useful tool in the study of disulfide proteins. Identify functional structural motifs from protein structures of unknown function becomes increasingly important in recent years due to the progress of the structural genomics projects. Though some structural patterns such as the Asp-His-Ser catalytic triad are easy to be detected because of their conserved residues and stringently constrained geometry, it is usually more challenging to detect a general structural motifs like, for example, the bba-metal binding motif, which has a much more variable conformation and sequence. At present, the identification of these motifs usually relies on manual procedures based on different structure and sequence analysis tools. In this study, we developed a structural alignment algorithm combining both structural and sequence information to identify the local structure motifs. We applied our method to two test cases: the bba-metal binding motif and the treble clef motif. The bba-metal binding motif plays an important role in non-specific DNA interactions and cleavage in host defense and apoptosis. The treble clef motif is a zinc-binding motif adaptable to diverse functions such as the binding of nucleic acid and hydrolysis of phosphodiester bonds. Our results are encouraging, indicating that we can effectively identify these structural motifs in an automatic fashion. Our method may provide a useful means for automatic functional annotation through detecting structural motifs associated with particular functions. Recently, Shih et al. have developed a method (Shih et al. Proteins: Structure, Function, and Bioinformatics 2007) to compute correlation of fluctuations. This method, referred to as the protein fixed-point model, is based on the positional vectors of atoms issuing from the fixed point, which is the point of the least fluctuations in proteins. One corollary from this model is that atoms lying on the same shell centered at the fixed point will have the same thermal fluctuations. In practice, this model provides a convenient way to compute the average dynamical properties of proteins directly from the geometrical shapes of proteins without the need of any mechanical models, and hence no trajectory integration or sophisticated matrix operations are needed. As a result, it is more efficient than molecular dynamics simulation or normal mode analysis. Though in the previous study the protein fixed-point model has been successfully applied to a number of proteins of various folds, it is not clear to what extent this model can be applied. In this report, we carried out comprehensive analysis of the protein fixed-point model for a dataset comprising high-resolution X-ray structures with pairwise sequence identity >=25%. We found that in most cases the protein fixed-point model works well. However, in case of proteins comprising multiple domains, each domain should be treated separately as an independent dynamical module with its own fixed point; and in case of the protein complex comprising a number of subunits, if functioning as a biological unit, the whole complex should be considered as one single dynamical module with one fixed point. Under such considerations, the resultant correlation coefficient between the computed and the X-ray structural B-factors for the data set is 0.59 and 75% (727/972) of proteins with a correlation coefficient >=0.5. Our result shows that the fixed-point model is indeed quite general and will be a useful tool for high throughput analysis of dynamical properties of proteins.
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Kamya, Petrina R. N. „Relationship between nucleic acid sequence, structure and function in terms of stabilizing interactions“. Thesis, 2009. http://spectrum.library.concordia.ca/976753/1/NR71159.pdf.

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The relationship between nucleic acid (NA) sequence, structure and function is intricately connected to the stabilizing interactions (primarily hydrogen bonding and 1t-stacking) that occur between the monomeric subunits that constitute NAs. Therefore, detailed insights into the. nature of the stabilizing interactions would permit the full exploitation of the structure-function relationship in NAs. A complete understanding of the role of the stabilizing interactions in NAs involves the fulfillment of two requirements: 1) The ability to determine the electronic structure of the monomeric units (in terms of the electron density distribution as an observable) that make up the fundamental structure of NAs, which is possible through the use of quantum chemical calculations, and 2) The ability to characterize the electronic structure of these monomeric units in the context of realistic NA structures. Ideally, such molecular structures are determined experimentally. These two ideas are combined into a methodology that has been designed, tested and validated in the work presented here. The proof of concept culminates in the ability of the methodology to exploit the structure-function relationship in NAs through procurement of full stabilization profiles of host NA and guest (small molecule inhibitors to the function of the NA) complexes, where the potential inhibitors were designed on the basis of the stabilization profiles of the host and natural ligand complexes
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27

蔡瑋芸. „Study and Analysis on Relationship between RNA Sequence and Secondary Structure by Computational Method“. Thesis, 2013. http://ndltd.ncl.edu.tw/handle/54319327438067774412.

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碩士
國立交通大學
生物資訊及系統生物研究所
101
Proteins play important roles in physiological reactions, biochemical syntheses and metabolism. For that, scientists often need to isolate the proteins for functional studies or therapeutic applications. However, preparations of a specific protein are often difficult to achieve from natural host cells. Therefore, it is usually necessary to utilize heterologous hosts to facilitate protein expression because of relative simplicity, low cost and fast high-density cultivation. Still, persistent challenges to the use of the heterologous host involve low level of expression for some proteins and then formation of inactive insoluble aggregates. In many cases, these problems can arise due to mRNA instability. This study has proposed methods utilizing thermodynamic parameters to analyze free energy variation in translational process. The aim of this work is to also solve the problem of gene expression in the heterologous host. Previous study revealed that ribosomal pausing could be engineered by alternative of RNA secondary structures. In this study, we have designed artificial RNA sequences and afterward verified its feasibility. We have also proposed a method for manipulating RNA sequences by computational methods that can be suitable for heterologous expression, in order to get target proteins successfully. This study has raised idea and practical methods to improve the heterologous expression of proteins, which may help the understanding of translation mechanism as well as understanding of the correlation between RNA secondary structure and protein folding. It can be further applied in the study of antibody, protein drugs, biomaterials and their corresponding applications.
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Puri, Kamal Deep. „Structure-Function Relationship Of Winged Bean (Psophocarpus Tetragonolobus) Basic Agglutinin (WBA I ) : Carbohydrate Binding, Domain Structure And Amino Acid Sequence Analysis“. Thesis, 1993. https://etd.iisc.ac.in/handle/2005/2440.

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29

Puri, Kamal Deep. „Structure-Function Relationship Of Winged Bean (Psophocarpus Tetragonolobus) Basic Agglutinin (WBA I ) : Carbohydrate Binding, Domain Structure And Amino Acid Sequence Analysis“. Thesis, 1993. http://etd.iisc.ernet.in/handle/2005/2440.

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30

Huang, Yu-Chieh, und 黃渝絜. „Studying the Membrane Spanning Region of Amyloid Precursor Protein and the Sequence/Structure Relationship of Prion Peptide Fibrils“. Thesis, 2017. http://ndltd.ncl.edu.tw/handle/2v9m8x.

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碩士
國立臺灣大學
生化科學研究所
105
In this paper, we undertook research into Alzheimers disease and Prion disease. The ratio of Aβ40 to Aβ42 depends on the cleavage site of γ-secretase in the transmembrane region of APP but it is not yet clear how γ-secretase chooses its cleavage site. In the transmembrane region of APP, there are four Gly arranged as GxxxGxxxGG. We proposed that these Gly residues might provide structural flexibility, thus allowing the whole membrane spanning region to behave like a spring. The structure of this region may also vary due to environmental changes. Furthermore, many studies have suggested that the composition of lipids in the membrane might also play an important role in Aβ production. Based on above considerations, we hypothesized that the cutting site of γ-secretase may vary because the membrane-spanning region of APP doesn’t form a typical α-helical structure and lipid composition may further affect its structure. Due to the difficulties of hydrophobic peptide purification, we focused on synthesizing and purifying a peptide corresponding to the sequence in the transmembrane region of APP and successfully got enough purified peptides in the study. In the future, we can use these peptides to prove our hypothesis. Many studies have shown that the prion protein sequence 108-144 (PrP108-144) is important to fibrillization and the cross-species infection of Prion disease as this PrP108-144 sequence is very similar amongst different mammalian prion proteins. In our study, we focused on the PrP108-144 sequence in humans, mice, and Syrian hamsters. The C-terminal residue 139 (according to the sequence from Syrian hamsters) from these three species is considered to be the key for fibrillization. To explore the relationship between the sequence and the structure of prion peptide fibrils formed by PrP108-144, we synthesized six different PrP108-144 peptides, including shaPrP(108-144), mPrP(107-143), huPrP(108-144), and the corresponding peptides with a H140→C mutation (for spin labeling). We used these wildtype peptides to form fibril seeds and used them to induce the spin-labeled peptides to form spin-labeled amyloid fibrils. We then compared their structures using Electron Spin Resonance (ESR) spectroscopy.
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31

Muralidhara, Chaitanya. „Matrix and tensor decomposition methods as tools to understanding sequence-structure relationships in sequence alignments“. 2010. http://hdl.handle.net/2152/9818.

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We describe the use of a tensor mode-1 higher-order singular value decomposition (HOSVD) in the analyses of alignments of 16S and 23S ribosomal RNA (rRNA) sequences, each encoded in a cuboid of frequencies of nucleotides across positions and organisms. This mode-1 HOSVD separates the data cuboids into combinations of patterns of nucleotide frequency variation across the positions and organisms, i.e., "eigenorganisms"' and corresponding nucleotide-specific segments of "eigenpositions," respectively, independent of a-priori knowledge of the taxonomic groups and their relationships, or the rRNA structures. We show that this mode-1 HOSVD provides a mathematical framework for modeling the sequence alignments where the mathematical variables, i.e., the significant eigenpositions and eigenorganisms, are consistent with current biological understanding of the 16S and 23S rRNAs. First, the significant eigenpositions identify multiple relations of similarity and dissimilarity among the taxonomic groups, some known and some previously unknown. Second, the corresponding eigenorganisms identify positions of nucleotides exclusively conserved within the corresponding taxonomic groups, but not among them, that map out entire substructures inserted or deleted within one taxonomic group relative to another. These positions are also enriched in adenosines that are unpaired in the rRNA secondary structure, the majority of which participate in tertiary structure interactions, and some also map to the same substructures. This demonstrates that an organism's evolutionary pathway is correlated and possibly also causally coordinated with insertions or deletions of entire rRNA substructures and unpaired adenosines, i.e., structural motifs which are involved in rRNA folding and function. Third, this mode-1 HOSVD reveals two previously unknown subgenic relationships of convergence and divergence between the Archaea and Microsporidia, that might correspond to two evolutionary pathways, in both the 16S and 23S rRNA alignments. This demonstrates that even on the level of a single rRNA molecule, an organism's evolutionary pathway is composed of different types of changes in structure in reaction to multiple concurrent evolutionary forces.
text
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32

Cheek, Sara Anne. „Exploring sequence-structure-function relationships in proteins using classification schemes“. 2005. http://edissertations.library.swmed.edu/pdf/CheekS121905/CheekSara.pdf.

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33

Zhao, Huiying. „Protein function prediction by integrating sequence, structure and binding affinity information“. Thesis, 2014. http://hdl.handle.net/1805/3913.

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Indiana University-Purdue University Indianapolis (IUPUI)
Proteins are nano-machines that work inside every living organism. Functional disruption of one or several proteins is the cause for many diseases. However, the functions for most proteins are yet to be annotated because inexpensive sequencing techniques dramatically speed up discovery of new protein sequences (265 million and counting) and experimental examinations of every protein in all its possible functional categories are simply impractical. Thus, it is necessary to develop computational function-prediction tools that complement and guide experimental studies. In this study, we developed a series of predictors for highly accurate prediction of proteins with DNA-binding, RNA-binding and carbohydrate-binding capability. These predictors are a template-based technique that combines sequence and structural information with predicted binding affinity. Both sequence and structure-based approaches were developed. Results indicate the importance of binding affinity prediction for improving sensitivity and precision of function prediction. Application of these methods to the human genome and structure genome targets demonstrated its usefulness in annotating proteins of unknown functions and discovering moon-lighting proteins with DNA,RNA, or carbohydrate binding function. In addition, we also investigated disruption of protein functions by naturally occurring genetic variations due to insertions and deletions (INDELS). We found that protein structures are the most critical features in recognising disease-causing non-frame shifting INDELs. The predictors for function predictions are available at http://sparks-lab.org/spot, and the predictor for classification of non-frame shifting INDELs is available at http://sparks-lab.org/ddig.
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34

Davison, Timothy Scott. „The p53 oligomerization domain : sequence-structure relationships and the design and characterization of altered oligomeric states“. 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=80295&T=F.

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35

Bedford, N. M., Zak E. Hughes, Z. Tang, Y. Li, B. D. Briggs, Y. Ren, M. T. Swihart et al. „Sequence-dependent structure/function relationships of catalytic peptide-enabled gold nanoparticles generated under ambient synthetic conditions“. 2015. http://hdl.handle.net/10454/15745.

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Yes
Peptide-enabled nanoparticle (NP) synthesis routes can create and/or assemble functional nanomaterials under environmentally friendly conditions, with properties dictated by complex interactions at the biotic/abiotic interface. Manipulation of this interface through sequence modification can provide the capability for material properties to be tailored to create enhanced materials for energy, catalysis, and sensing applications. Fully realizing the potential of these materials requires a comprehensive understanding of sequence-dependent structure/function relationships that is presently lacking. In this work, the atomic-scale structures of a series of peptide-capped Au NPs are determined using a combination of atomic pair distribution function analysis of high-energy X-ray diffraction data and advanced molecular dynamics (MD) simulations. The Au NPs produced with different peptide sequences exhibit varying degrees of catalytic activity for the exemplar reaction 4-nitrophenol reduction. The experimentally derived atomic-scale NP configurations reveal sequence-dependent differences in structural order at the NP surface. Replica exchange with solute-tempering MD simulations are then used to predict the morphology of the peptide overlayer on these Au NPs and identify factors determining the structure/catalytic properties relationship. We show that the amount of exposed Au surface, the underlying surface structural disorder, and the interaction strength of the peptide with the Au surface all influence catalytic performance. A simplified computational prediction of catalytic performance is developed that can potentially serve as a screening tool for future studies. Our approach provides a platform for broadening the analysis of catalytic peptide-enabled metallic NP systems, potentially allowing for the development of rational design rules for property enhancemen
Air Force Office for Scientific Research (Grant #FA9550-12-1-0226, RRN; AFOSR LRIR) and DOE-BES grant DE-SC0006877, fellowship support from the National Research Council Research Associateship
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Bäumlová, Adriana. „Exprese a charakterisace homologů lidské glutamát karboxypeptidasy II“. Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-308278.

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English abstract Glutamate carboxypeptidase II (GCPII, EC 3.4.17.21) is a membrane bound glycoprotein that belongs to the metallopeptidase M28 family. Two physiological substrates were found for GCPII. The first one, N-acetyl-aspartylglutamate (NAAG), serves as a neurotransmiter in the brain and GCPII hydrolyzes it to yield free glutamate in the synaptic cleft. Excess glutamate might be cytotoxic and eventually lead to excitoxic nerve cells death. Inhibition of NAAG hydrolyzing activity has been shown to be neuroprotective. Therefore, GCPII inhibition was suggested as a therapeutic target in treatment of neurological disorders where excess glutamate is involved. The second substrate, polyglutamyl folate, is a precursor of folic acid which is required for cell growth and development. GCPII cleaves off glutamate from dietary folates and thus facilitates their absorption in small intestine. Although GCPII biological relevance is known only in the brain and the small intestine, its role in the prostate is also important. GCPII has been described as a prostate cancer marker as it is expressed on the membrane of prostate cancer cells. Since GCPII is type II transmembrane protein, it is enzymatically active and undergoes internalization, it has been suggested as a promising tool for specific anticancer-drug...
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