1vkj

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spinqualitylabelsall models 1vkj, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of heparan sulfate 3-O-sulfotransferase isoform 1 in the presence of PAP

Overview

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

1VKJ is a Single protein structure of sequence from Mus musculus with SO4 and A3P as ligands. This structure superseeds 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.

Reference

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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