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| | ==Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.== | | ==Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.== |
| - | <StructureSection load='3ptz' size='340' side='right' caption='[[3ptz]], [[Resolution|resolution]] 2.50Å' scene=''> | + | <StructureSection load='3ptz' size='340' side='right'caption='[[3ptz]], [[Resolution|resolution]] 2.50Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3ptz]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PTZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PTZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3ptz]] 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=3PTZ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PTZ FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UDX:URIDINE-5-DIPHOSPHATE-XYLOPYRANOSE'>UDX</scene><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]] 2.5Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3prj|3prj]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=UDX:URIDINE-5-DIPHOSPHATE-XYLOPYRANOSE'>UDX</scene></td></tr> |
| - | <tr><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 Homo sapiens])</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=3ptz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ptz OCA], [https://pdbe.org/3ptz PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ptz RCSB], [https://www.ebi.ac.uk/pdbsum/3ptz PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ptz ProSAT]</span></td></tr> |
| - | <tr><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>
| + | </table> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ptz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ptz OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3ptz RCSB], [http://www.ebi.ac.uk/pdbsum/3ptz PDBsum]</span></td></tr> | + | == Function == |
| - | <table> | + | [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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| | Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.,Kadirvelraj R, Sennett NC, Polizzi SJ, Weitzel S, Wood ZA Biochemistry. 2011 Jun 3. PMID:21595445<ref>PMID:21595445</ref> | | Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.,Kadirvelraj R, Sennett NC, Polizzi SJ, Weitzel S, Wood ZA Biochemistry. 2011 Jun 3. PMID:21595445<ref>PMID:21595445</ref> |
| | | | |
| - | 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 3ptz" style="background-color:#fffaf0;"></div> |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| - | [[Category: UDP-glucose 6-dehydrogenase]] | + | [[Category: Large Structures]] |
| - | [[Category: Kadirvelraj, R.]] | + | [[Category: Kadirvelraj R]] |
| - | [[Category: Wood, Z A.]] | + | [[Category: Wood ZA]] |
| - | [[Category: Cytosol]]
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| - | [[Category: Feedback inhibition]]
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| - | [[Category: Nad binding protein]]
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| - | [[Category: Nucleotide sugar dehydrogenase]]
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| - | [[Category: Oxidoreductase]]
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| - | [[Category: Rossmann fold]]
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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
Allosteric feedback inhibition is the mechanism by which metabolic end products regulate their own biosynthesis by binding to an upstream enzyme. Despite its importance in controlling metabolism, there are relatively few allosteric mechanisms understood in detail. This is because allostery does not have an identifiable structural motif, making the discovery of new allosteric enzymes a difficult process. The lack of a conserved motif implies that the evolution of each allosteric mechanism is unique. Here we describe an atypical allosteric mechanism in human UDP-alpha-d-glucose 6-dehydrogenase (hUGDH) based on an easily acquired and identifiable structural attribute: packing defects in the protein core. In contrast to classic allostery, the active and allosteric sites in hUGDH are present as a single, bifunctional site. Using two new crystal structures, we show that binding of the feedback inhibitor, UDP-alpha-d-xylose, elicits a distinct induced-fit response; a buried loop translates approximately 4 A along and rotates approximately 180 degrees about the main chain axis, requiring surrounding side chains to repack. This allosteric transition is facilitated by packing defects, which negate the steric conformational restraints normally imposed by the protein core. Sedimentation velocity studies show that this repacking favors the formation of an inactive hexameric complex with unusual symmetry. We present evidence that hUGDH and the unrelated enzyme dCTP deaminase have converged to very similar atypical allosteric mechanisms using the same adaptive strategy, the selection for packing defects. Thus, the selection for packing defects is a robust mechanism for the evolution of allostery and induced fit.
Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase.,Kadirvelraj R, Sennett NC, Polizzi SJ, Weitzel S, Wood ZA Biochemistry. 2011 Jun 3. PMID:21595445[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kadirvelraj R, Sennett NC, Polizzi SJ, Weitzel S, Wood ZA. Role of Packing Defects in the Evolution of Allostery and Induced Fit in Human UDP-Glucose Dehydrogenase. Biochemistry. 2011 Jun 3. PMID:21595445 doi:10.1021/bi2005637
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