View source for 3uan


==Crystal structure of 3-O-sulfotransferase (3-OST-1) with bound PAP and heptasaccharide substrate==
<StructureSection load='3uan' size='340' side='right'caption='[[3uan]], [[Resolution|resolution]] 1.84&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3uan]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3UAN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3UAN FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.844&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A3P:ADENOSINE-3-5-DIPHOSPHATE'>A3P</scene>, <scene name='pdbligand=BDP:BETA-D-GLUCOPYRANURONIC+ACID'>BDP</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=NGY:2-(ACETYLAMINO)-2-DEOXY-6-O-SULFO-ALPHA-D-GLUCOPYRANOSE'>NGY</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3uan FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3uan OCA], [https://pdbe.org/3uan PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3uan RCSB], [https://www.ebi.ac.uk/pdbsum/3uan PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3uan ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/HS3S1_MOUSE HS3S1_MOUSE] Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) to catalyze the transfer of a sulfo group to position 3 of glucosamine residues in heparan. Catalyzes the rate limiting step in the biosynthesis of heparan sulfate (HSact). This modification is a crucial step in the biosynthesis of anticoagulant heparan sulfate as it completes the structure of the antithrombin pentasaccharide binding site.<ref>PMID:9346953</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heparin is a polysaccharide-based natural product that is used clinically as an anticoagulant drug. Heparan sulfate 3-O-sulfotransferase (3-OST) is an enzyme that transfers a sulfo group to the 3-OH position of a glucosamine unit. 3-OST is present in multiple isoforms, and the polysaccharides modified by these different isoforms perform distinct biological functions. 3-OST isoform 1 (3-OST-1) is the key enzyme for the biosynthesis of anticoagulant heparin. Here, we report the crystal structure of the ternary complex of 3-OST-1, 3'-phosphoadenosine 5'-phosphate, and a heptasaccharide substrate. Comparisons to previously determined structures of 3-OST-3 reveal unique binding modes used by the different isoforms of 3-OST for distinguishing the fine structures of saccharide substrates. Our data demonstrate that the saccharide substrates display distinct conformations when interacting with the different 3-OST isoforms. Site-directed mutagenesis data suggest that several key amino residues, including Lys259, Thr256, and Trp283 in 3-OST-3 and Arg268 in 3-OST-1, play important roles in substrate binding and specificity between isoforms. These results deepen our understanding of the biosynthetic mechanism of heparan sulfate and provide structural information for engineering enzymes for an enhanced biosynthetic approach to heparin production.

Dissecting the substrate recognition of 3-O-sulfotransferase for the biosynthesis of anticoagulant heparin.,Moon AF, Xu Y, Woody SM, Krahn JM, Linhardt RJ, Liu J, Pedersen LC Proc Natl Acad Sci U S A. 2012 Mar 19. PMID:22431632<ref>PMID:22431632</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3uan" style="background-color:#fffaf0;"></div>

==See Also==
*[[Sulfotransferase 3D structures|Sulfotransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Krahn JM]]
[[Category: Linhardt RJ]]
[[Category: Liu J]]
[[Category: Moon AF]]
[[Category: Pedersen LC]]
[[Category: Woody SM]]
[[Category: Xu Y]]