View source for 4pxq

==Crystal structure of D-glucuronyl C5-epimerase in complex with heparin hexasaccharide==
<StructureSection load='4pxq' size='340' side='right' caption='[[4pxq]], [[Resolution|resolution]] 2.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4pxq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PXQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PXQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=UAP:4-DEOXY-2-O-SULFO-ALPHA-L-THREO-HEX-4-ENOPYRANURONIC+ACID'>UAP</scene>, <scene name='pdbligand=IDS:2-O-SULFO-ALPHA-L-IDOPYRANURONIC+ACID'>IDS</scene>, <scene name='pdbligand=SGN:N,O6-DISULFO-GLUCOSAMINE'>SGN</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4pw2|4pw2]]</td></tr>
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Heparosan-N-sulfate-glucuronate_5-epimerase Heparosan-N-sulfate-glucuronate 5-epimerase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=5.1.3.17 5.1.3.17] </span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4pxq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4pxq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4pxq RCSB], [http://www.ebi.ac.uk/pdbsum/4pxq PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Heparan sulfate (HS) is a glycosaminoglycan present on the cell surface and in the extracellular matrix which interacts with diverse signal molecules and is essential for many physiological processes including embryonic development, cell growth, inflammation, and blood coagulation. D-glucuronyl C5-epimerase (Glce) is a crucial enzyme in HS synthesis, converting D-glucuronic acid (GlcA) to L-iduronic acid (IdoA) to increase HS flexibility. This modification of HS is important for protein ligand recognition. We have determined the crystal structures of Glce in apo form (unliganded) and in complex with heparin hexasaccharide (product of Glce following O-sulfation), both in a stable dimer conformation. A Glce dimer contains two catalytic sites, each at a positively charged cleft in C-terminal alpha-helical domains binding one negatively charged hexasaccharide. Based on the structural and mutagenesis studies, three tyrosine residues, Y468, Y528, and Y546 in the active site were found to be crucial for the enzymatic activity. The complex structure also reveals the mechanism of product inhibition, i.e. 2-O- and 6-O-sulfation of HS keeps the C5 carbon of IdoA away from the active-site tyrosine residues. Our structural and functional data advance understanding of the key modification regulation in HS biosynthesis.

Structural and functional study of D-glucuronyl C5-epimerase.,Qin Y, Ke J, Gu X, Fang J, Wang W, Cong Q, Li J, Tan J, Brunzelle JS, Zhang C, Jiang Y, Melcher K, Li JP, Xu HE, Ding K J Biol Chem. 2015 Jan 7. pii: jbc.M114.602201. PMID:25568314<ref>PMID:25568314</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Heparosan-N-sulfate-glucuronate 5-epimerase]]
[[Category: Brunzelle, J S]]
[[Category: Ding, K]]
[[Category: Gu, X]]
[[Category: Ke, J]]
[[Category: Qin, Y]]
[[Category: Tan, J]]
[[Category: Xu, H E]]
[[Category: Epimerization enzyme]]
[[Category: Heparan sulfate]]
[[Category: Heparan sulfate c5-epimerase]]
[[Category: Heparin]]
[[Category: Isomerase]]
[[Category: Multiple domain structure]]