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| | ==Human UDP-Glucose Dehydrogenase with UDP-Xylose Bound to the Co-enzyme Site== | | ==Human UDP-Glucose Dehydrogenase with UDP-Xylose Bound to the Co-enzyme Site== |
| - | <StructureSection load='5vr8' size='340' side='right' caption='[[5vr8]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='5vr8' size='340' side='right'caption='[[5vr8]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5vr8]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5VR8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5VR8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5vr8]] is a 6 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=5VR8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5VR8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=UDX:URIDINE-5-DIPHOSPHATE-XYLOPYRANOSE'>UDX</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]] 1.999Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">UGDH ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=UDX:URIDINE-5-DIPHOSPHATE-XYLOPYRANOSE'>UDX</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=5vr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vr8 OCA], [https://pdbe.org/5vr8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5vr8 RCSB], [https://www.ebi.ac.uk/pdbsum/5vr8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5vr8 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=5vr8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5vr8 OCA], [http://pdbe.org/5vr8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5vr8 RCSB], [http://www.ebi.ac.uk/pdbsum/5vr8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5vr8 ProSAT]</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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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: UDP-glucose 6-dehydrogenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Beattie, N R]] | + | [[Category: Beattie NR]] |
| - | [[Category: Kadirvelraj, R]] | + | [[Category: Kadirvelraj R]] |
| - | [[Category: Wood, Z A]] | + | [[Category: Wood ZA]] |
| - | [[Category: Hugdh]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Udp-glucose dehydrogenase]]
| + | |
| - | [[Category: Udp-xylose]]
| + | |
| - | [[Category: Udx]]
| + | |
| Structural highlights
Function
UGDH_HUMAN Involved in the biosynthesis of glycosaminoglycans; hyaluronan, chondroitin sulfate, and heparan sulfate.
Publication Abstract from PubMed
Protein structures are dynamic and can explore a large conformational landscape(1,2). Only some of these structural substates are important for protein function (such as ligand binding, catalysis and regulation)(3-5). How evolution shapes the structural ensemble to optimize a specific function is poorly understood(3,4). One of the constraints on the evolution of proteins is the stability of the folded 'native' state. Despite this, 44% of the human proteome contains intrinsically disordered peptide segments greater than 30 residues in length(6), the majority of which have no known function(7-9). Here we show that the entropic force produced by an intrinsically disordered carboxy terminus (ID-tail) shifts the conformational ensemble of human UDP-alpha-D-glucose-6-dehydrogenase (UGDH) towards a substate with a high affinity for an allosteric inhibitor. The function of the ID-tail does not depend on its sequence or chemical composition. Instead, the affinity enhancement can be accurately predicted based on the length of the intrinsically disordered segment, and is consistent with the entropic force generated by an unstructured peptide attached to the protein surface(10-13). Our data show that the unfolded state of the ID-tail rectifies the dynamics and structure of UGDH to favour inhibitor binding. Because this entropic rectifier does not have any sequence or structural constraints, it is an easily acquired adaptation. This model implies that evolution selects for disordered segments to tune the energy landscape of proteins, which may explain the persistence of intrinsic disorder in the proteome.
The entropic force generated by intrinsically disordered segments tunes protein function.,Keul ND, Oruganty K, Schaper Bergman ET, Beattie NR, McDonald WE, Kadirvelraj R, Gross ML, Phillips RS, Harvey SC, Wood ZA Nature. 2018 Nov;563(7732):584-588. doi: 10.1038/s41586-018-0699-5. Epub 2018 Nov, 12. PMID:30420606[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Keul ND, Oruganty K, Schaper Bergman ET, Beattie NR, McDonald WE, Kadirvelraj R, Gross ML, Phillips RS, Harvey SC, Wood ZA. The entropic force generated by intrinsically disordered segments tunes protein function. Nature. 2018 Nov;563(7732):584-588. doi: 10.1038/s41586-018-0699-5. Epub 2018 Nov, 12. PMID:30420606 doi:http://dx.doi.org/10.1038/s41586-018-0699-5
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