2YDQ

CpOGA D298N in complex with hOGA-derived O-GlcNAc peptide

Summary for 2YDQ

• Entry DOI: 10.2210/pdb2ydq/pdb
• Related: 2CBI 2CBJ 2J62 2JH2 2V5C 2V5D 2VUR 2WB5 2X0Y 2XPK 2YDR 2YDS
• Descriptor: O-GLCNACASE NAGJ, BIFUNCTIONAL PROTEIN NCOAT, CADMIUM ION, ... (5 entities in total)
• Functional Keywords: hydrolase-peptide complex, hydrolase/peptide
• Biological source: CLOSTRIDIUM PERFRINGENS; More
• Cellular location: Isoform 3: Nucleus. Isoform 1: Cytoplasm: O60502
• Total number of polymer chains: 2
• Total formula weight: 69157.78

Authors

Schimpl, M.,Borodkin, V.S.,Gray, L.J.,van Aalten, D.M.F. (deposition date: 2011-03-24, release date: 2012-03-14, Last modification date: 2020-07-29)

Primary citation

Schimpl, M.,Borodkin, V.S.,Gray, L.J.,Van Aalten, D.M.F.
Synergy of Peptide and Sugar in O-Glcnacase Substrate Recognition.
Chem.Biol., 19:173-, 2012

PubMed Abstract: Protein O-GlcNAcylation is an essential reversible posttranslational modification in higher eukaryotes. O-GlcNAc addition and removal is catalyzed by O-GlcNAc transferase and O-GlcNAcase, respectively. We report the molecular details of the interaction of a bacterial O-GlcNAcase homolog with three different synthetic glycopeptides derived from characterized O-GlcNAc sites in the human proteome. Strikingly, the peptides bind a conserved O-GlcNAcase substrate binding groove with similar orientation and conformation. In addition to extensive contacts with the sugar, O-GlcNAcase recognizes the peptide backbone through hydrophobic interactions and intramolecular hydrogen bonds, while avoiding interactions with the glycopeptide side chains. These findings elucidate the molecular basis of O-GlcNAcase substrate specificity, explaining how a single enzyme achieves cycling of the complete O-GlcNAc proteome. In addition, this work will aid development of O-GlcNAcase inhibitors that target the peptide binding site.

PubMed: 22365600
DOI: 10.1016/J.CHEMBIOL.2012.01.011

Experimental method

X-RAY DIFFRACTION (2.6 Å)