4d11 | pdb_00004d11
GalNAc-T2 crystal soaked with UDP-5SGalNAc, mEA2 peptide and manganese (Lower resolution dataset)
Structural highlights
FunctionGALT2_HUMAN Catalyzes the initial reaction in O-linked oligosaccharide biosynthesis, the transfer of an N-acetyl-D-galactosamine residue to a serine or threonine residue on the protein receptor. Has a broad spectrum of substrates for peptides such as EA2, Muc5AC, Muc1a, Muc1b. Probably involved in O-linked glycosylation of the immunoglobulin A1 (IgA1) hinge region.[1] [2] Publication Abstract from PubMedThe retaining glycosyltransferase GalNAc-T2 is a member of a large family of human polypeptide GalNAc-transferases that is responsible for the post-translational modification of many cell-surface proteins. By the use of combined structural and computational approaches, we provide the first set of structural snapshots of the enzyme during the catalytic cycle and combine these with quantum-mechanics/molecular-mechanics (QM/MM) metadynamics to unravel the catalytic mechanism of this retaining enzyme at the atomic-electronic level of detail. Our study provides a detailed structural rationale for an ordered bi-bi kinetic mechanism and reveals critical aspects of substrate recognition, which dictate the specificity for acceptor Thr versus Ser residues and enforce a front-face SN i-type reaction in which the substrate N-acetyl sugar substituent coordinates efficient glycosyl transfer. Substrate-Guided Front-Face Reaction Revealed by Combined Structural Snapshots and Metadynamics for the Polypeptide N-Acetylgalactosaminyltransferase 2.,Lira-Navarrete E, Iglesias-Fernandez J, Zandberg WF, Companon I, Kong Y, Corzana F, Pinto BM, Clausen H, Peregrina JM, Vocadlo DJ, Rovira C, Hurtado-Guerrero R Angew Chem Int Ed Engl. 2014 Jun 20. doi: 10.1002/anie.201402781. PMID:24954443[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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