1vkj: Difference between revisions
New page: left|200px<br /><applet load="1vkj" size="450" color="white" frame="true" align="right" spinBox="true" caption="1vkj, resolution 2.50Å" /> '''Crystal structure of... |
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[[Image:1vkj.gif|left|200px]]<br /><applet load="1vkj" size=" | [[Image:1vkj.gif|left|200px]]<br /><applet load="1vkj" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1vkj, resolution 2.50Å" /> | caption="1vkj, resolution 2.50Å" /> | ||
'''Crystal structure of heparan sulfate 3-O-sulfotransferase isoform 1 in the presence of PAP'''<br /> | '''Crystal structure of heparan sulfate 3-O-sulfotransferase isoform 1 in the presence of PAP'''<br /> | ||
==Overview== | ==Overview== | ||
Heparan sulfate interacts with antithrombin, a protease inhibitor, to | Heparan sulfate interacts with antithrombin, a protease inhibitor, to regulate blood coagulation. Heparan sulfate 3-O-sulfotransferase isoform 1 performs the crucial last step modification in the biosynthesis of anticoagulant heparan sulfate. This enzyme transfers the sulfuryl group (SO(3)) from 3'-phosphoadenosine 5'-phosphosulfate to the 3-OH position of a glucosamine residue to form the 3-O-sulfo glucosamine, a structural motif critical for binding of heparan sulfate to antithrombin. In this study, we report the crystal structure of 3-O-sulfotransferase isoform 1 at 2.5-A resolution in a binary complex with 3'-phosphoadenosine 5'-phosphate. This structure reveals residues critical for 3'-phosphoadenosine 5'-phosphosulfate binding and suggests residues required for the binding of heparan sulfate. In addition, site-directed mutagenesis analyses suggest that residues Arg-67, Lys-68, Arg-72, Glu-90, His-92, Asp-95, Lys-123, and Arg-276 are essential for enzymatic activity. Among these essential amino acid residues, we find that residues Arg-67, Arg-72, His-92, and Asp-95 are conserved in heparan sulfate 3-O-sulfotransferases but not in heparan N-deacetylase/N-sulfotransferase, suggesting a role for these residues in conferring substrate specificity. Results from this study provide information essential for understanding the biosynthesis of anticoagulant heparan sulfate and the general mechanism of action of heparan sulfate sulfotransferases. | ||
==About this Structure== | ==About this Structure== | ||
1VKJ 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 SO4 and A3P as [http://en.wikipedia.org/wiki/ligands ligands]. This structure | 1VKJ 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=SO4:'>SO4</scene> and <scene name='pdbligand=A3P:'>A3P</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. This structure supersedes the now removed PDB entry 1S6T. Active as [http://en.wikipedia.org/wiki/[Heparan_sulfate]-glucosamine_3-sulfotransferase_1 [Heparan sulfate]-glucosamine 3-sulfotransferase 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.8.2.23 2.8.2.23] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1VKJ OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: [Heparan sulfate]-glucosamine 3-sulfotransferase 1]] | [[Category: [Heparan sulfate]-glucosamine 3-sulfotransferase 1]] | ||
[[Category: Lee, K | [[Category: Lee, K A.]] | ||
[[Category: Linhardt, R | [[Category: Linhardt, R J.]] | ||
[[Category: Liu, J.]] | [[Category: Liu, J.]] | ||
[[Category: Negishi, M.]] | [[Category: Negishi, M.]] | ||
[[Category: Pedersen, L | [[Category: Pedersen, L C.]] | ||
[[Category: Thorp, S.]] | [[Category: Thorp, S.]] | ||
[[Category: A3P]] | [[Category: A3P]] | ||
| Line 27: | Line 27: | ||
[[Category: sulfotransferase]] | [[Category: sulfotransferase]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:36:17 2008'' | ||
Revision as of 16:36, 21 February 2008
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Crystal structure of heparan sulfate 3-O-sulfotransferase isoform 1 in the presence of PAP
OverviewOverview
Heparan sulfate interacts with antithrombin, a protease inhibitor, to regulate blood coagulation. Heparan sulfate 3-O-sulfotransferase isoform 1 performs the crucial last step modification in the biosynthesis of anticoagulant heparan sulfate. This enzyme transfers the sulfuryl group (SO(3)) from 3'-phosphoadenosine 5'-phosphosulfate to the 3-OH position of a glucosamine residue to form the 3-O-sulfo glucosamine, a structural motif critical for binding of heparan sulfate to antithrombin. In this study, we report the crystal structure of 3-O-sulfotransferase isoform 1 at 2.5-A resolution in a binary complex with 3'-phosphoadenosine 5'-phosphate. This structure reveals residues critical for 3'-phosphoadenosine 5'-phosphosulfate binding and suggests residues required for the binding of heparan sulfate. In addition, site-directed mutagenesis analyses suggest that residues Arg-67, Lys-68, Arg-72, Glu-90, His-92, Asp-95, Lys-123, and Arg-276 are essential for enzymatic activity. Among these essential amino acid residues, we find that residues Arg-67, Arg-72, His-92, and Asp-95 are conserved in heparan sulfate 3-O-sulfotransferases but not in heparan N-deacetylase/N-sulfotransferase, suggesting a role for these residues in conferring substrate specificity. Results from this study provide information essential for understanding the biosynthesis of anticoagulant heparan sulfate and the general mechanism of action of heparan sulfate sulfotransferases.
About this StructureAbout this Structure
1VKJ is a Single protein structure of sequence from Mus musculus with and as ligands. This structure supersedes the now removed PDB entry 1S6T. Active as [Heparan_sulfate-glucosamine_3-sulfotransferase_1 [Heparan sulfate]-glucosamine 3-sulfotransferase 1], with EC number 2.8.2.23 Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure and mutational analysis of heparan sulfate 3-O-sulfotransferase isoform 1., Edavettal SC, Lee KA, Negishi M, Linhardt RJ, Liu J, Pedersen LC, J Biol Chem. 2004 Jun 11;279(24):25789-97. Epub 2004 Apr 1. PMID:15060080 [[Category: [Heparan sulfate]-glucosamine 3-sulfotransferase 1]]
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