1XHB

The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1

Summary for 1XHB

• Entry DOI: 10.2210/pdb1xhb/pdb
• Descriptor: Polypeptide N-acetylgalactosaminyltransferase 1, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, MANGANESE (II) ION, ... (5 entities in total)
• Functional Keywords: glycosyltransferase-a (gt-a), transferase
• Biological source: Mus musculus (house mouse)
• Cellular location: Polypeptide N- acetylgalactosaminyltransferase 1: Golgi apparatus, Golgi stack membrane ; Single-pass type II membrane protein . Polypeptide N- acetylgalactosaminyltransferase 1 soluble form: Secreted : O08912
• Total number of polymer chains: 1
• Total formula weight: 54958.52

Authors

Fritz, T.A.,Hurley, J.H.,Trinh, L.B.,Shiloach, J.,Tabak, L.A. (deposition date: 2004-09-17, release date: 2004-10-26, Last modification date: 2024-11-13)

Primary citation

Fritz, T.A.,Hurley, J.H.,Trinh, L.B.,Shiloach, J.,Tabak, L.A.
The beginnings of mucin biosynthesis: The crystal structure of UDP-GalNAc:polypeptide {alpha}-N-acetylgalactosaminyltransferase-T1
Proc.Natl.Acad.Sci.USA, 101:15307-15312, 2004

PubMed Abstract: 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.

PubMed: 15486088
DOI: 10.1073/pnas.0405657101

Experimental method

X-RAY DIFFRACTION (2.5 Å)