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

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.

SUBMITTER: Borodkin VS 

PROVIDER: S-EPMC3927924 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature