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| | ==Crystal Structure of Unliganded, Full Length hUGDH at pH 7.0== | | ==Crystal Structure of Unliganded, Full Length hUGDH at pH 7.0== |
| - | <StructureSection load='4rjt' size='340' side='right' caption='[[4rjt]], [[Resolution|resolution]] 2.70Å' scene=''> | + | <StructureSection load='4rjt' size='340' side='right'caption='[[4rjt]], [[Resolution|resolution]] 2.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4rjt]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJT OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4RJT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4rjt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RJT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RJT FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4qej|4qej]], [[3prj|3prj]], [[3ptz|3ptz]], [[3tf5|3tf5]], [[2q3e|2q3e]], [[2qg4|2qg4]]</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr> |
| - | <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>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rjt OCA], [https://pdbe.org/4rjt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rjt RCSB], [https://www.ebi.ac.uk/pdbsum/4rjt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rjt ProSAT]</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=4rjt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rjt OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4rjt RCSB], [http://www.ebi.ac.uk/pdbsum/4rjt PDBsum]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate. | + | [https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4rjt" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: UDP-glucose 6-dehydrogenase]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Sidlo, A M]] | + | [[Category: Large Structures]] |
| - | [[Category: Wood, Z A]] | + | [[Category: Sidlo AM]] |
| - | [[Category: Cytosol]] | + | [[Category: Wood ZA]] |
| - | [[Category: Nad binding]]
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| - | [[Category: Nucleotide sugar 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-glucose binding]]
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| Structural highlights
Function
UGDH_HUMAN Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kadirvelraj R, Custer GS, Keul ND, Sennett NC, Sidlo AM, Walsh RM Jr, Wood ZA. Hysteresis in Human UDP-Glucose Dehydrogenase Is Due to a Restrained Hexameric Structure That Favors Feedback Inhibition. Biochemistry. 2014 Dec 30;53(51):8043-51. doi: 10.1021/bi500594x. Epub 2014 Dec, 18. PMID:25478983 doi:http://dx.doi.org/10.1021/bi500594x
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