1xhb
From Proteopedia
(New page: 200px<br /><applet load="1xhb" size="450" color="white" frame="true" align="right" spinBox="true" caption="1xhb, resolution 2.50Å" /> '''The Crystal Structur...) |
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| - | [[Image:1xhb.gif|left|200px]]<br /><applet load="1xhb" size=" | + | [[Image:1xhb.gif|left|200px]]<br /><applet load="1xhb" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1xhb, resolution 2.50Å" /> | caption="1xhb, resolution 2.50Å" /> | ||
'''The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1'''<br /> | '''The Crystal Structure of UDP-GalNAc: polypeptide alpha-N-acetylgalactosaminyltransferase-T1'''<br /> | ||
==Overview== | ==Overview== | ||
| - | UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases | + | 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== | ==About this Structure== | ||
| - | 1XHB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with MN and CA as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] Full crystallographic information is available from [http:// | + | 1XHB is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=MN:'>MN</scene> and <scene name='pdbligand=CA:'>CA</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Polypeptide_N-acetylgalactosaminyltransferase Polypeptide N-acetylgalactosaminyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.1.41 2.4.1.41] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XHB OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Polypeptide N-acetylgalactosaminyltransferase]] | [[Category: Polypeptide N-acetylgalactosaminyltransferase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| - | [[Category: Fritz, T | + | [[Category: Fritz, T A.]] |
| - | [[Category: Hurley, J | + | [[Category: Hurley, J H.]] |
[[Category: Shiloach, J.]] | [[Category: Shiloach, J.]] | ||
| - | [[Category: Tabak, L | + | [[Category: Tabak, L A.]] |
| - | [[Category: Trinh, L | + | [[Category: Trinh, L B.]] |
[[Category: CA]] | [[Category: CA]] | ||
[[Category: MN]] | [[Category: MN]] | ||
[[Category: glycosyltransferase-a (gt-a)]] | [[Category: glycosyltransferase-a (gt-a)]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:54:53 2008'' |
Revision as of 13:54, 21 February 2008
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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 and 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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