4AY5

Human O-GlcNAc transferase (OGT) in complex with UDP and glycopeptide

Summary for 4AY5

• Entry DOI: 10.2210/pdb4ay5/pdb
• Related: 1W3B 4AY6
• Descriptor: UDP-N-ACETYLGLUCOSAMINE--PEPTIDE N-ACETYLGLUCOSAMINYL TRANSFERASE 110 KDA SUBUNIT, GTAB1TIDE, URIDINE-5'-DIPHOSPHATE, ... (4 entities in total)
• Functional Keywords: transferase-peptide complex, transferase, glycosyl transferase, trimeric product complex, o-glcnac, transferase/peptide
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 8
• Total formula weight: 330884.30

Authors

Schimpl, M.,Zheng, X.,Blair, D.E.,Schuettelkopf, A.W.,Navratilova, I.,Aristotelous, T.,Ferenbach, A.T.,Macnaughtan, M.A.,Borodkin, V.S.,van Aalten, D.M.F. (deposition date: 2012-06-18, release date: 2012-10-24, Last modification date: 2024-11-13)

Primary citation

Schimpl, M.,Zheng, X.,Borodkin, V.S.,Blair, D.E.,Ferenbach, A.T.,Schuettelkopf, A.W.,Navratilova, I.,Aristotelous, T.,Albarbarawi, O.,Robinson, D.A.,Macnaughtan, M.A.,Van Aalten, D.M.F.
O-Glcnac Transferase Invokes Nucleotide Sugar Pyrophosphate Participation in Catalysis
Nat.Chem.Biol., 8:969-, 2012

PubMed Abstract: Protein O-GlcNAcylation is an essential post-translational modification on hundreds of intracellular proteins in metazoa, catalyzed by O-linked β-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 α-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.

PubMed: 23103942
DOI: 10.1038/NCHEMBIO.1108

Experimental method

X-RAY DIFFRACTION (3.15 Å)