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| | <StructureSection load='1xpm' size='340' side='right'caption='[[1xpm]], [[Resolution|resolution]] 1.60Å' scene=''> | | <StructureSection load='1xpm' size='340' side='right'caption='[[1xpm]], [[Resolution|resolution]] 1.60Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1xpm]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Staphylococcus_aureus_aureus Staphylococcus aureus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XPM OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1XPM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1xpm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Staphylococcus_aureus Staphylococcus aureus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1XPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1XPM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=HMG:3-HYDROXY-3-METHYLGLUTARYL-COENZYME+A'>HMG</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]] 1.6Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=SCY:S-ACETYL-CYSTEINE'>SCY</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CAA:ACETOACETYL-COENZYME+A'>CAA</scene>, <scene name='pdbligand=HMG:3-HYDROXY-3-METHYLGLUTARYL-COENZYME+A'>HMG</scene>, <scene name='pdbligand=SCY:S-ACETYL-CYSTEINE'>SCY</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1xpk|1xpk]], [[1xpl|1xpl]]</div></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=1xpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xpm OCA], [https://pdbe.org/1xpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1xpm RCSB], [https://www.ebi.ac.uk/pdbsum/1xpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1xpm ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">mvaS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=46170 Staphylococcus aureus aureus])</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_synthase Hydroxymethylglutaryl-CoA synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.3.10 2.3.3.10] </span></td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1xpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1xpm OCA], [http://pdbe.org/1xpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1xpm RCSB], [http://www.ebi.ac.uk/pdbsum/1xpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1xpm ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [https://www.uniprot.org/uniprot/A0A0H3K1U2_STAAW A0A0H3K1U2_STAAW] |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Hydroxymethylglutaryl-CoA synthase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Staphylococcus aureus aureus]] | + | [[Category: Staphylococcus aureus]] |
| - | [[Category: Campobasso, N]] | + | [[Category: Campobasso N]] |
| - | [[Category: Harrison, D H.T]] | + | [[Category: Harrison DHT]] |
| - | [[Category: Misra, I]] | + | [[Category: Misra I]] |
| - | [[Category: Miziorko, H M]] | + | [[Category: Miziorko HM]] |
| - | [[Category: Saadat, D]] | + | [[Category: Saadat D]] |
| - | [[Category: Theisen, M J]] | + | [[Category: Theisen MJ]] |
| - | [[Category: Cholesterol biosynthesis]]
| + | |
| - | [[Category: Coenzyme some]]
| + | |
| - | [[Category: Condensing enzyme]]
| + | |
| - | [[Category: Hmg]]
| + | |
| - | [[Category: Hmg-coa synthase]]
| + | |
| - | [[Category: Thiolase fold]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
A0A0H3K1U2_STAAW
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The formation of carbon-carbon bonds via an acyl-enzyme intermediate plays a central role in fatty acid, polyketide, and isoprenoid biosynthesis. Uniquely among condensing enzymes, 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGS) catalyzes the formation of a carbon-carbon bond by activating the methyl group of an acetylated cysteine. This reaction is essential in Gram-positive bacteria, and represents the first committed step in human cholesterol biosynthesis. Reaction kinetics, isotope exchange, and mass spectroscopy suggest surprisingly that HMGS is able to catalyze the "backwards" reaction in solution, where HMG-CoA is cleaved to form acetoacetyl-CoA (AcAc-CoA) and acetate. Here, we trap a complex of acetylated HMGS from Staphylococcus aureus and bound acetoacetyl-CoA by cryo-cooling enzyme crystals at three different times during the course of its back-reaction with its physiological product (HMG-CoA). This nonphysiological "backwards" reaction is used to understand the details of the physiological reaction with regards to individual residues involved in catalysis and substrate/product binding. The structures suggest that an active-site glutamic acid (Glu-79) acts as a general base both in the condensation between acetoacetyl-CoA and the acetylated enzyme, and the hydrolytic release of HMG-CoA from the enzyme. The ability to trap this enzyme-intermediate complex may suggest a role for protein dynamics and the interplay between protomers during the normal course of catalysis.
3-hydroxy-3-methylglutaryl-CoA synthase intermediate complex observed in "real-time".,Theisen MJ, Misra I, Saadat D, Campobasso N, Miziorko HM, Harrison DH Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16442-7. Epub 2004 Oct 21. PMID:15498869[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Theisen MJ, Misra I, Saadat D, Campobasso N, Miziorko HM, Harrison DH. 3-hydroxy-3-methylglutaryl-CoA synthase intermediate complex observed in "real-time". Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16442-7. Epub 2004 Oct 21. PMID:15498869
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