O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis

TY - JOUR

T1 - O-GlcNAc transferase invokes nucleotide sugar pyrophosphate participation in catalysis

AU - Schimpl, Marianne

AU - Zheng, Xiaowei

AU - Borodkin, Vladimir S.

AU - Blair, David E.

AU - Ferenbach, Andrew T.

AU - Schüttelkopf, Alexander W.

AU - Navratilova, Iva

AU - Aristotelous, Tonia

AU - Albarbarawi, Osama

AU - Robinson, David A.

AU - van Aalten, Daan M.F.

AU - Macnaughtan, Megan A.

N1 - Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2012

Y1 - 2012

N2 - Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor a-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.

AB - Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked ß-N-acetylglucosamine (O-GlcNAc) transferase (OGT) using unknown mechanisms of transfer and substrate recognition. Through crystallographic snapshots and mechanism-inspired chemical probes, we define how human OGT recognizes the sugar donor and acceptor peptide and uses a new catalytic mechanism of glycosyl transfer, involving the sugar donor a-phosphate as the catalytic base as well as an essential lysine. This mechanism seems to be a unique evolutionary solution to the spatial constraints imposed by a bulky protein acceptor substrate and explains the unexpected specificity of a recently reported metabolic OGT inhibitor.

UR - https://www.scopus.com/pages/publications/84870384002

U2 - 10.1038/nchembio.1108

DO - 10.1038/nchembio.1108

M3 - Article

C2 - 23103942

SN - 1552-4450

JO - Nature Chemical Biology

JF - Nature Chemical Biology

ER -