QM/MM Molecular Dynamics Study of the O-GlcNAc Transferase Reaction Mechanism

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F14%3A00079602" target="_blank" >RIV/00216224:14740/14:00079602 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

QM/MM Molecular Dynamics Study of the O-GlcNAc Transferase Reaction Mechanism

Popis výsledku v původním jazyce

Glycosylation is one of the important post-translational modifications that provide greater proteomic diversity This event is also critical for a wide range of biological processes, such as cell adhesion, defense mechanism, cell proliferation, cancer metastasis etc through variety of glycoconjugates. These glycoconjugates are formed by glycosyltransferases which add saccharides onto proteins, lipids sugars etc. Here we are exploring the reaction mechanisms of O-GlcNAc transferase (OGTs), where GlcNAc istransferred to ?OH group of Ser/Thr of the proteins. Three groups have proposed mechanisms on different crystal structures of OGTs, suggesting different catalytic base to abstract proton from Ser, 1) His498[1], 2) alpha-phosphate[2], and 3) water molecule shunting[3] , but still the process is not clear. In presented study we were trying to confirm one of the proposed mechanisms employing hybrid QM/MM CPMD molecular dynamics. We have modelled all three proposed mechanisms.

Název v anglickém jazyce

QM/MM Molecular Dynamics Study of the O-GlcNAc Transferase Reaction Mechanism

Popis výsledku anglicky

Glycosylation is one of the important post-translational modifications that provide greater proteomic diversity This event is also critical for a wide range of biological processes, such as cell adhesion, defense mechanism, cell proliferation, cancer metastasis etc through variety of glycoconjugates. These glycoconjugates are formed by glycosyltransferases which add saccharides onto proteins, lipids sugars etc. Here we are exploring the reaction mechanisms of O-GlcNAc transferase (OGTs), where GlcNAc istransferred to ?OH group of Ser/Thr of the proteins. Three groups have proposed mechanisms on different crystal structures of OGTs, suggesting different catalytic base to abstract proton from Ser, 1) His498[1], 2) alpha-phosphate[2], and 3) water molecule shunting[3] , but still the process is not clear. In presented study we were trying to confirm one of the proposed mechanisms employing hybrid QM/MM CPMD molecular dynamics. We have modelled all three proposed mechanisms.

Druh

O - Ostatní výsledky

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

<a href="/cs/project/LH13055" target="_blank" >LH13055: Multidisciplinární přístup k návrhu léčiv - Inhibice proteinů s návazností na cukry</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů