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| | ==HMG-CoA Reductase from Pseudomonas mevalonii complexed with NAD and intermediate hemiacetal form of HMG-CoA== | | ==HMG-CoA Reductase from Pseudomonas mevalonii complexed with NAD and intermediate hemiacetal form of HMG-CoA== |
| - | <StructureSection load='4i4b' size='340' side='right' caption='[[4i4b]], [[Resolution|resolution]] 1.70Å' scene=''> | + | <StructureSection load='4i4b' size='340' side='right'caption='[[4i4b]], [[Resolution|resolution]] 1.70Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i4b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/'pseudomonas_mevalonii' 'pseudomonas mevalonii']. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I4B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I4B FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i4b]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Pseudomonas_mevalonii Pseudomonas mevalonii]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I4B OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I4B FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=1CO:(3S)-3-HYDROXY-3-METHYL-5-SULFANYLPENTANOIC+ACID'>1CO</scene>, <scene name='pdbligand=1CV:(3R,5R,9R,19R,21S)-1-[(2R,3S,4R,5R)-5-(6-AMINO-9H-PURIN-9-YL)-4-HYDROXY-3-(PHOSPHONOOXY)TETRAHYDROFURAN-2-YL]-3,5,9,21-TETRAHYDROXY-8,8,21-TRIMETHYL-10,14-DIOXO-19-SULFANYL-2,4,6-TRIOXA-18-THIA-11,15-DIAZA-3,5-DIPHOSPHATRICOSAN-23-OIC+ACID+3,5-DIOXIDE'>1CV</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.7Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4i56|4i56]], [[4i64|4i64]], [[4i6a|4i6a]], [[4i6w|4i6w]], [[4i6y|4i6y]], [[1qax|1qax]], [[1qay|1qay]], [[1r31|1r31]], [[1r71|1r71]], [[1t02|1t02]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=1CO:(3S)-3-HYDROXY-3-METHYL-5-SULFANYLPENTANOIC+ACID'>1CO</scene>, <scene name='pdbligand=1CV:(3R,5R,9R,19R,21S)-1-[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-4-hydroxy-3-(phosphonooxy)tetrahydrofuran-2-yl]-3,5,9,21-tetrahydroxy-8,8,21-trimethyl-10,14-dioxo-19-sulfanyl-2,4,6-trioxa-18-thia-11,15-diaza-3,5-diphosphatricosan-23-oic+acid+3,5-dioxide'>1CV</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAD:NICOTINAMIDE-ADENINE-DINUCLEOTIDE'>NAD</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mvaA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=32044 'Pseudomonas mevalonii'])</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=4i4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i4b OCA], [https://pdbe.org/4i4b PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i4b RCSB], [https://www.ebi.ac.uk/pdbsum/4i4b PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i4b ProSAT]</span></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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4i4b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i4b OCA], [http://pdbe.org/4i4b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i4b RCSB], [http://www.ebi.ac.uk/pdbsum/4i4b PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i4b ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/MVAA_PSEMV MVAA_PSEMV]] P.mevalonii can use mevalonate as sole carbon source. With this enzyme mevalonate is deacetylated to HMG-CoA. | + | [https://www.uniprot.org/uniprot/MVAA_PSEMV MVAA_PSEMV] P.mevalonii can use mevalonate as sole carbon source. With this enzyme mevalonate is deacetylated to HMG-CoA. |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | In this study we take advantage of the ability of HMG-CoA reductase (HMGR) from Pseudomonas mevalonii to remain active while in crystallized form to study the changing interactions between the ligands and protein as the first reaction intermediate is created. HMG-CoA reductase catalyzes one of the few double oxidation/reduction reactions in intermediary metabolism that take place in a single active site. Our laboratory has undertaken an exploration of this reaction space using structures of HMG-CoA reductase complexed with various substrate, nucleotide, product, and inhibitor combinations. Focusing in this publication on the first hydride transfer, our structures follow this reduction reaction as the enzyme converts the HMG-CoA thioester from a flat sp2 like geometry to a pyramidal thiohemiacetal configuration consistent with a transition to an sp3 orbital. This change in the geometry propagates through the CoA ligand whose first amide bond is rotated 180 degrees where it anchors a web of hydrogen bonds that weave together the nucleotide, the reaction intermediate, the enzyme and the catalytic residues. This creates a stable intermediate structure prepared for nucleotide exchange and the second reduction reaction within the HMG-CoA reductase active site. Identification of this reaction intermediate provides a template for the development of an inhibitor that would act as an antibiotic effective against the HMG-CoA reductase of methicillin-resistant Staphylococcus aureus.
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| - | A novel role for CoA during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase.,Steussy CN, Critchelow CJ, Schmidt TJ, Min JK, Wrensford LV, Burgner JW, Rodwell VW, Stauffacher CV Biochemistry. 2013 Jun 26. PMID:23802607<ref>PMID:23802607</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4i4b" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[HMG-CoA Reductase|HMG-CoA Reductase]] | + | *[[HMG-CoA Reductase 3D structures|HMG-CoA Reductase 3D structures]] |
| - | == References ==
| + | |
| - | <references/>
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Pseudomonas mevalonii]] | | [[Category: Pseudomonas mevalonii]] |
| - | [[Category: Hydroxymethylglutaryl-CoA reductase]]
| + | [[Category: Burgner JW]] |
| - | [[Category: Burgner, J W]] | + | [[Category: Critchelow CJ]] |
| - | [[Category: Critchelow, C J]] | + | [[Category: Min J]] |
| - | [[Category: Min, J]] | + | [[Category: Rodwell VW]] |
| - | [[Category: Rodwell, V W]] | + | [[Category: Schmidt T]] |
| - | [[Category: Schmidt, T]] | + | [[Category: Stauffacher CV]] |
| - | [[Category: Stauffacher, C V]] | + | [[Category: Steussy CN]] |
| - | [[Category: Steussy, C N]] | + | [[Category: Wrensford LV]] |
| - | [[Category: Wrensford, L V]] | + | |
| - | [[Category: Oxidoreductase]]
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