1xhb
From Proteopedia
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[[Image:1xhb.gif|left|200px]] | [[Image:1xhb.gif|left|200px]] | ||
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'''The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1''' | '''The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1''' | ||
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[[Category: Tabak, L A.]] | [[Category: Tabak, L A.]] | ||
[[Category: Trinh, L B.]] | [[Category: Trinh, L B.]] | ||
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Revision as of 12:01, 3 May 2008
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. 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 Page seeded by OCA on Sat May 3 15:01:49 2008