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| - | ==Structure of Apo hUGDH==
| + | #REDIRECT [[5w4x]] This PDB entry is obsolete and replaced by 5w4x |
| - | <StructureSection load='4qej' size='340' side='right' caption='[[4qej]], [[Resolution|resolution]] 2.65Å' scene=''>
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| - | == Structural highlights ==
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| - | <table><tr><td colspan='2'>[[4qej]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4QEJ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4QEJ FirstGlance]. <br>
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| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=PE4:2-{2-[2-(2-{2-[2-(2-ETHOXY-ETHOXY)-ETHOXY]-ETHOXY}-ETHOXY)-ETHOXY]-ETHOXY}-ETHANOL'>PE4</scene></td></tr>
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| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2q3e|2q3e]], [[2qg4|2qg4]], [[3prj|3prj]], [[3ptz|3ptz]], [[3tf5|3tf5]]</td></tr>
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| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/UDP-glucose_6-dehydrogenase UDP-glucose 6-dehydrogenase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.22 1.1.1.22] </span></td></tr>
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| - | <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=4qej FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4qej OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4qej RCSB], [http://www.ebi.ac.uk/pdbsum/4qej PDBsum]</span></td></tr>
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| - | </table>
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| - | == Function ==
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| - | [[http://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
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| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Human UDP-alpha-d-glucose-6-dehydrogenase (hUGDH) displays hysteresis because of a slow isomerization from an inactive state (E*) to an active state (E). Here we show that the structure of E* constrains hUGDH in a conformation that favors feedback inhibition at physiological pH. The feedback inhibitor UDP-alpha-d-xylose (UDP-Xyl) competes with the substrate UDP-alpha-d-glucose for the active site. Upon binding, UDP-Xyl triggers an allosteric switch that changes the structure and affinity of the intersubunit interface to form a stable but inactive horseshoe-shaped hexamer. Using sedimentation velocity studies and a new crystal structure, we show that E* represents a stable conformational intermediate between the active and feedback-inhibited conformations. Because the allosteric switch occludes the cofactor and substrate binding sites in the inactive hexamer, the intermediate conformation observed in the crystal structure is consistent with the E* transient observed in relaxation studies. Steady-state analysis shows that the E* conformation enhances the affinity of hUGDH for the allosteric inhibitor UDP-Xyl by 8.6-fold (Ki = 810 nM). We present a model in which the constrained quaternary structure permits a small effector molecule to leverage a disproportionately large allosteric response.
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| - | Hysteresis in Human UDP-Glucose Dehydrogenase Is Due to a Restrained Hexameric Structure That Favors Feedback Inhibition.,Kadirvelraj R, Custer GS, Keul ND, Sennett NC, Sidlo AM, Walsh RM Jr, Wood ZA Biochemistry. 2014 Dec 30;53(51):8043-51. doi: 10.1021/bi500594x. Epub 2014 Dec, 18. PMID:25478983<ref>PMID:25478983</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| - | == References ==
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| - | <references/>
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| - | __TOC__
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| - | </StructureSection>
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| - | [[Category: UDP-glucose 6-dehydrogenase]]
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| - | [[Category: Custer, G S]]
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| - | [[Category: Sennett, N C]]
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| - | [[Category: Wood, Z A]]
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| - | [[Category: Cytosol]]
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| - | [[Category: Dehydrogenase]]
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| - | [[Category: Oxidation]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Rossmann fold]]
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| - | [[Category: Udp-glucuronic acid]]
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| - | [[Category: Udp-sugar binding]]
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