1xhb
From Proteopedia
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The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1
Overview
UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases, (ppGaNTases) initiate the formation of mucin-type, O-linked glycans by, catalyzing the transfer of alpha-N-acetylgalactosamine from UDP-GalNAc to, Ser or Thr residues of core proteins to form the Tn antigen, (GalNAc-alpha-1-O-Ser/Thr). ppGaNTases are unique among, glycosyltransferases in containing a C-terminal lectin domain. We present, the x-ray crystal structure of a ppGaNTase, murine ppGaNTase-T1, and show, that it folds to form distinct catalytic and lectin domains. The, association of the two domains forms a large cleft in the surface of the, enzyme that contains a Mn2+ ion complexed by invariant D209 and H211 of, the "DXH" motif and by invariant H344. Each of the three potential lectin, domain carbohydrate-binding sites (alpha, beta, and gamma) is located on, the active-site face of the enzyme, suggesting a mechanism by which the, transferase may accommodate multiple conformations of glycosylated, acceptor substrates. A model of a mucin 1 glycopeptide substrate bound to, the enzyme shows that the spatial separation between the lectin alpha site, and a modeled active site UDP-GalNAc is consistent with the in vitro, pattern of glycosylation observed for this peptide catalyzed by, ppGaNTase-T1. The structure also provides a template for the larger, ppGaNTase family, and homology models of several ppGaNTase isoforms, predict dramatically different surface chemistries consistent with, isoform-selective acceptor substrate recognition.
About this Structure
1XHB is a Single protein structure of sequence from Mus musculus with MN and CA as ligands. Active as Polypeptide N-acetylgalactosaminyltransferase, with EC number 2.4.1.41 Full crystallographic information is available from OCA.
Reference
The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase-T1., Fritz TA, Hurley JH, Trinh LB, Shiloach J, Tabak LA, Proc Natl Acad Sci U S A. 2004 Oct 26;101(43):15307-12. Epub 2004 Oct 14. PMID:15486088
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