View source for 6om8


==Caenorhabditis Elegans UDP-Glucose Dehydrogenase in complex with UDP-Xylose==
<StructureSection load='6om8' size='340' side='right'caption='[[6om8]], [[Resolution|resolution]] 2.45&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6om8]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Caenorhabditis_elegans Caenorhabditis elegans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6OM8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OM8 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]] 2.449&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UDX:URIDINE-5-DIPHOSPHATE-XYLOPYRANOSE'>UDX</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=6om8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6om8 OCA], [https://pdbe.org/6om8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6om8 RCSB], [https://www.ebi.ac.uk/pdbsum/6om8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6om8 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/UGDH_CAEEL UGDH_CAEEL] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Human UDP-glucose dehydrogenase (hUGDH) oxidizes uridine diphosphate (UDP)-glucose to UDP-glucuronic acid, an essential substrate in the phase II metabolism of drugs. The activity of hUGDH is controlled by an atypical allosteric mechanism in which the feedback inhibitor UDP-xylose competes with the substrate for the active site and triggers a buried allosteric switch to produce an inactive complex (E(Omega)). Previous comparisons with a nonallosteric UGDH identified six large-to-small substitutions that produce packing defects in the protein core and provide the conformational flexibility necessary for the allosteric transition. Here, we test the hypothesis that these large-to-small substitutions form a motif that can be used to identify allosteric UGDHs. Caenorhabditis elegans UGDH (cUGDH) conserves this motif with the exception of an Ala-to-Pro substitution in position 109. The crystal structures of unliganded and UDP-xylose bound cUGDH show that the A109P substitution is accommodated by an Asn-to-Ser substitution at position 290. Steady-state analysis and sedimentation velocity studies show that the allosteric transition is conserved in cUGDH. The enzyme also exhibits hysteresis in progress curves and negative cooperativity with respect to NAD(+) binding. Both of these phenomena are conserved in the human enzyme, which is strong evidence that these represent fundamental features of atypical allostery in UGDH. A phylogenetic analysis of UGDH shows that the atypical allostery motif is ancient and identifies a potential transition point in the evolution of the UGDH family.

Conservation of Atypical Allostery in C. elegans UDP-Glucose Dehydrogenase.,Beattie NR, Keul ND, Hicks Sirmans TN, McDonald WE, Talmadge TM, Taujale R, Kannan N, Wood ZA ACS Omega. 2019 Sep 24;4(15):16318-16329. doi: 10.1021/acsomega.9b01565., eCollection 2019 Oct 8. PMID:31616809<ref>PMID:31616809</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6om8" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Caenorhabditis elegans]]
[[Category: Large Structures]]
[[Category: Beattie NR]]
[[Category: Hicks Sirmans TN]]
[[Category: McDonald WE]]
[[Category: Wood ZA]]