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| <StructureSection load='6eev' size='340' side='right'caption='[[6eev]], [[Resolution|resolution]] 1.49Å' scene=''> | | <StructureSection load='6eev' size='340' side='right'caption='[[6eev]], [[Resolution|resolution]] 1.49Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6eev]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/"pseudomonas_desmolytica"_gray_and_thornton_1928 "pseudomonas desmolytica" gray and thornton 1928]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EEV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6EEV FirstGlance]. <br> | | <table><tr><td colspan='2'>[[6eev]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Delftia_acidovorans Delftia acidovorans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6EEV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6EEV FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MEV:(R)-MEVALONATE'>MEV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=SUC:SUCROSE'>SUC</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]] 1.49Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Daci_0287 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=80866 "Pseudomonas desmolytica" Gray and Thornton 1928])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FRU:FRUCTOSE'>FRU</scene>, <scene name='pdbligand=GLC:ALPHA-D-GLUCOSE'>GLC</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MEV:(R)-MEVALONATE'>MEV</scene>, <scene name='pdbligand=PRD_900003:sucrose'>PRD_900003</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Hydroxymethylglutaryl-CoA_reductase Hydroxymethylglutaryl-CoA reductase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.1.1.88 1.1.1.88] </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=6eev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eev OCA], [https://pdbe.org/6eev PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6eev RCSB], [https://www.ebi.ac.uk/pdbsum/6eev PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6eev 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=6eev FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6eev OCA], [http://pdbe.org/6eev PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6eev RCSB], [http://www.ebi.ac.uk/pdbsum/6eev PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6eev ProSAT]</span></td></tr> | |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
| | == Function == |
| == Publication Abstract from PubMed == | | [https://www.uniprot.org/uniprot/A9BQX8_DELAS A9BQX8_DELAS] |
| The enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (HMGR) catalyzes the first committed step of the mevalonate pathway, which is used across biology in the biosynthesis of countless metabolites. HMGR consumes 2 equiv of the cofactor NAD(P)H to perform the four-electron reduction of HMG-CoA to mevalonate toward the production of steroids and isoprenoids, the largest class of natural products. Recent structural data have shown that HMGR contains a highly mobile C-terminal domain (CTD) that is believed to adopt many different conformations to permit binding and dissociation of the substrate, cofactors, and products at specific points during the reaction cycle. Here, we have characterized the HMGR from Delftia acidovorans as an NADH-specific enzyme and determined crystal structures of the enzyme in unbound, mevalonate-bound, and NADH- and citrate-bound states. Together, these structures depict ligand binding in both the active site and the cofactor-binding site while illustrating how a conserved helical motif confers NAD(P)H cofactor specificity. Unexpectedly, the NADH-bound structure also reveals a new conformation of the CTD, in which the domain has "flipped" upside-down, while directly binding the cofactor. By capturing these structural snapshots, this work not only expands the known range of HMGR domain movement but also provides valuable insight into the catalytic mechanism of this biologically important enzyme.
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| New Crystallographic Snapshots of Large Domain Movements in Bacterial 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase.,Ragwan ER, Arai E, Kung Y Biochemistry. 2018 Sep 19. doi: 10.1021/acs.biochem.8b00869. PMID:30199631<ref>PMID:30199631</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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| <div class="pdbe-citations 6eev" style="background-color:#fffaf0;"></div>
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| ==See Also== | | ==See Also== |
| *[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]] | | *[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]] |
| == References ==
| |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Pseudomonas desmolytica gray and thornton 1928]] | | [[Category: Delftia acidovorans]] |
| [[Category: Hydroxymethylglutaryl-CoA reductase]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Arai, E]] | | [[Category: Arai E]] |
| [[Category: Kung, Y]] | | [[Category: Kung Y]] |
| [[Category: Ragwan, E R]] | | [[Category: Ragwan ER]] |
| [[Category: Mevalonate pathway]]
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| [[Category: Oxidoreductase]]
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