2d7i
From Proteopedia
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Crsytal structure of pp-GalNAc-T10 with UDP, GalNAc and Mn2+
Overview
Mucin-type O-glycans are important carbohydrate chains involved in, differentiation and malignant transformation. Biosynthesis of the O-glycan, is initiated by the transfer of N-acetylgalactosamine (GalNAc) which is, catalyzed by UDP-GalNAc:polypeptide, alpha-N-acetylgalactosaminyltransferases (pp-GalNAc-Ts). Here we present, crystal structures of the pp-GalNAc-T10 isozyme, which has specificity for, glycosylated peptides, in complex with the hydrolyzed donor substrate, UDP-GalNAc and in complex with GalNAc-serine. A structural comparison with, uncomplexed pp-GalNAc-T1 suggests that substantial conformational changes, occur in two loops near the catalytic center upon donor substrate binding, and that a distinct interdomain arrangement between the catalytic and, lectin domains forms a narrow cleft for acceptor substrates. The distance, between the catalytic center and the carbohydrate-binding site on the, lectin beta sub-domain influences the position of GalNAc glycosylation on, GalNAc-glycosylated peptide substrates. A chimeric enzyme in which the two, domains of pp-GalNAc-T10 are connected by a linker from pp-GalNAc-T1, acquires activity toward non-glycosylated acceptors, identifying a, potential mechanism for generating the various acceptor specificities in, different isozymes to produce a wide range of O-glycans.
About this Structure
2D7I is a Single protein structure of sequence from Homo sapiens with NAG, NGA, MN and UDP as ligands. Active as Polypeptide N-acetylgalactosaminyltransferase, with EC number 2.4.1.41 Full crystallographic information is available from OCA.
Reference
Structural basis of carbohydrate transfer activity by human UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T10)., Kubota T, Shiba T, Sugioka S, Furukawa S, Sawaki H, Kato R, Wakatsuki S, Narimatsu H, J Mol Biol. 2006 Jun 9;359(3):708-27. Epub 2006 Apr 19. PMID:16650853
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