Docking study of the potential glycosyltransferase inhibitors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14310%2F09%3A00039161" target="_blank" >RIV/00216224:14310/09:00039161 - 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

Docking study of the potential glycosyltransferase inhibitors

Popis výsledku v původním jazyce

Glycosyltransferases are involved in the biosynthesis of glycans, which play an important role in many biological events. The N-acetylglucosaminyltransferase I catalyzes the transfer of a GlcNAc residue from the donor UDP-GlcNAc to the acceptor, which isthe C2-hydroxyl group of a mannose residue in the trimannosyl core of the Man5GlcNAc2-Asn-X oligosaccharide. Previous molecular modeling studies determined the structure of a transition state (TS) for the enzymatic reaction catalyzed by GnT-I. The proposed scaffold uses the alkylthio and phosphonate groups linked to the anomeric centre of five-member ring to mimic the arrangement of GlcNAc, UDP and acceptor in TS. The conformational properties of the analogue were investigated by DFT(B3LYP) methods using Schrödinger software packages. a- and b- anomers of the stable conformer were docked into crystal structure of GnT-I (PDB code 1FOA) using the Glide software. The binding energy was computed using the Liaison software.

Název v anglickém jazyce

Docking study of the potential glycosyltransferase inhibitors

Popis výsledku anglicky

Glycosyltransferases are involved in the biosynthesis of glycans, which play an important role in many biological events. The N-acetylglucosaminyltransferase I catalyzes the transfer of a GlcNAc residue from the donor UDP-GlcNAc to the acceptor, which isthe C2-hydroxyl group of a mannose residue in the trimannosyl core of the Man5GlcNAc2-Asn-X oligosaccharide. Previous molecular modeling studies determined the structure of a transition state (TS) for the enzymatic reaction catalyzed by GnT-I. The proposed scaffold uses the alkylthio and phosphonate groups linked to the anomeric centre of five-member ring to mimic the arrangement of GlcNAc, UDP and acceptor in TS. The conformational properties of the analogue were investigated by DFT(B3LYP) methods using Schrödinger software packages. a- and b- anomers of the stable conformer were docked into crystal structure of GnT-I (PDB code 1FOA) using the Glide software. The binding energy was computed using the Liaison software.

Druh

O - Ostatní výsledky

CEP obor

CF - Fyzikální chemie a teoretická chemie

OECD FORD obor

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Projekt

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Návaznosti

S - Specificky vyzkum na vysokych skolach

Rok uplatnění

2009

Kód důvěrnosti údajů

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