Bisubstrate UDP–peptide conjugates as human O-GlcNAc transferase inhibitors-Reference-Cited by-同舟云学术

Bisubstrate UDP–peptide conjugates as human O-GlcNAc transferase inhibitors

Published:2014-01-10 Issue:3 Volume:457 Page:497-502
ISSN:0264-6021
Container-title:Biochemical Journal
language:en
Short-container-title:

Author:

Borodkin Vladimir S.¹,Schimpl Marianne¹,Gundogdu Mehmet¹,Rafie Karim¹,Dorfmueller Helge C.¹²,Robinson David A.³,van Aalten Daan M. F.¹²

Affiliation:

1. MRC Protein Phosphorylation und Ubiquitylation Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.

2. Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.

3. Drug Discovery Unit, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, U.K.

Abstract

Inhibitors of OGT (O-GlcNAc transferase) are valuable tools to study the cell biology of protein O-GlcNAcylation. We report OGT bisubstrate-linked inhibitors (goblins) in which the acceptor serine in the peptide VTPVSTA is covalently linked to UDP, eliminating the GlcNAc pyranoside ring. Goblin1 co-crystallizes with OGT, revealing an ordered C3 linker and retained substrate-binding modes, and binds the enzyme with micromolar affinity, inhibiting glycosyltransfer on to protein and peptide substrates.

Publisher

Portland Press Ltd.

Subject

Cell Biology,Molecular Biology,Biochemistry

Link

https://portlandpress.com/biochemj/article-pdf/457/3/497/678310/bj4570497.pdf

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