Substrate Assisted Catalytic Mechanism of O GlcNAc Transferase Discovered by Quantum Mechanics/Molecular Mechanics Investigation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F12%3A00064660" target="_blank" >RIV/00216224:14740/12:00064660 - isvavai.cz</a>

Výsledek na webu

<a href="http://pubs.acs.org/doi/abs/10.1021/ja307040m" target="_blank" >http://pubs.acs.org/doi/abs/10.1021/ja307040m</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/ja307040m" target="_blank" >10.1021/ja307040m</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Substrate Assisted Catalytic Mechanism of O GlcNAc Transferase Discovered by Quantum Mechanics/Molecular Mechanics Investigation

Popis výsledku v původním jazyce

In higher eukaryotes, a variety of proteins are post-translationally modified by adding O-linked N-acetylglucosamine (GlcNAc) residue to serine or threonine residues. Misregulation of O-GlcNAcylation is linked to a wide variety of diseases, such as diabetes, cancer, and neurodegenerative diseases, including Alzheimer's disease. GlcNAc transfer is catalyzed by an inverting glycosyltransferase O-GlcNAc transferase (uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetylaminyltransferase, OGT) thatbelongs to the GT-B superfamily. The catalytic mechanism of this metal-independent glycosyltransferase is of primary importance and is investigated here using QM(DFT)/MM methods. The structural model of the reaction site used in this paper is based on the crystal structures of OGT. The entire enzyme substrate system was partitioned into two different subsystems: the QM subsystem containing 198 atoms, and the MM region containing 11 326 atoms.

Název v anglickém jazyce

Substrate Assisted Catalytic Mechanism of O GlcNAc Transferase Discovered by Quantum Mechanics/Molecular Mechanics Investigation

Popis výsledku anglicky

In higher eukaryotes, a variety of proteins are post-translationally modified by adding O-linked N-acetylglucosamine (GlcNAc) residue to serine or threonine residues. Misregulation of O-GlcNAcylation is linked to a wide variety of diseases, such as diabetes, cancer, and neurodegenerative diseases, including Alzheimer's disease. GlcNAc transfer is catalyzed by an inverting glycosyltransferase O-GlcNAc transferase (uridine diphospho-N-acetylglucosamine:polypeptide beta-N-acetylaminyltransferase, OGT) thatbelongs to the GT-B superfamily. The catalytic mechanism of this metal-independent glycosyltransferase is of primary importance and is investigated here using QM(DFT)/MM methods. The structural model of the reaction site used in this paper is based on the crystal structures of OGT. The entire enzyme substrate system was partitioned into two different subsystems: the QM subsystem containing 198 atoms, and the MM region containing 11 326 atoms.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2012

Kód důvěrnosti údajů

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

Název periodika

J. Am. Chem. Soc.

ISSN

0002-7863

e-ISSN

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Svazek periodika

134

Číslo periodika v rámci svazku

37

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

15563-15571

Kód UT WoS článku

000308830600067

EID výsledku v databázi Scopus

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