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4edf

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Current revision (14:58, 14 March 2024) (edit) (undo)
 
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== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[4edf]] is a 4 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=4EDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
<table><tr><td colspan='2'>[[4edf]] is a 4 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=4EDF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EDF FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</scene></td></tr>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.08&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=UPG:URIDINE-5-DIPHOSPHATE-GLUCOSE'>UPG</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [https://pdbe.org/4edf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [https://www.ebi.ac.uk/pdbsum/4edf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</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=4edf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4edf OCA], [https://pdbe.org/4edf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4edf RCSB], [https://www.ebi.ac.uk/pdbsum/4edf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4edf ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
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[[https://www.uniprot.org/uniprot/UGDH_HUMAN UGDH_HUMAN]] Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
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[https://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 dehydrogenase (hUGDH) catalyzes the NAD(+)-dependent oxidation of UDP-alpha-d-glucose (UDG) to produce UDP-alpha-d-glucuronic acid. The oligomeric structure of hUGDH is dynamic and can form two distinct hexameric complexes in solution. The active form of hUGDH consists of dimers that undergo a concentration-dependent association to form a hexamer with 32 symmetry. In the presence of the allosteric feedback inhibitor UDP-alpha-d-xylose (UDX), hUGDH changes shape to form an inactive, horseshoe-shaped complex. Previous studies have identified the UDX-induced allosteric mechanism that changes the hexameric structure to inhibit the enzyme. Here, we investigate the role of the 32 symmetry hexamer in the catalytic cycle. We engineered a stable hUGDH dimer by introducing a charge-switch substitution (K94E) in the hexamer-building interface (hUGDH(K94E)). The k(cat) of hUGDH(K94E) is approximately 160-fold lower than that of the wild-type enzyme, suggesting that the hexamer is the catalytically relevant state. We also show that cofactor binding triggers the formation of the 32 symmetry hexamer, but UDG is needed for the stability of the complex. The hUGDH(K94E) crystal structure at 2.08 A resolution identifies loop(88-110) as the cofactor-responsive allosteric switch that drives hexamer formation; loop(88-110) directly links cofactor binding to the stability of the hexamer-building interface. In the interface, loop(88-110) packs against the Thr131-loop/alpha6 helix, the allosteric switch that responds to the feedback inhibitor UDX. We also identify a structural element (the S-loop) that explains the indirect stabilization of the hexamer by substrate and supports a sequential, ordered binding of the substrate and cofactor. These observations support a model in which (i) UDG binds to the dimer and stabilizes the S-loop to promote cofactor binding and (ii) cofactor binding orders loop(88-110) to induce formation of the catalytically active hexamer.
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Cofactor Binding Triggers a Molecular Switch To Allosterically Activate Human UDP-alpha-d-glucose 6-Dehydrogenase.,Sennett NC, Kadirvelraj R, Wood ZA Biochemistry. 2012 Nov 20;51(46):9364-74. doi: 10.1021/bi301067w. Epub 2012 Nov, 8. PMID:23106432<ref>PMID:23106432</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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<div class="pdbe-citations 4edf" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
__TOC__
</StructureSection>
</StructureSection>

Current revision

Dimeric hUGDH, K94E

PDB ID 4edf

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