1x9e
From Proteopedia
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|PDB= 1x9e |SIZE=350|CAPTION= <scene name='initialview01'>1x9e</scene>, resolution 2.40Å | |PDB= 1x9e |SIZE=350|CAPTION= <scene name='initialview01'>1x9e</scene>, resolution 2.40Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=SO4:SULFATE ION'>SO4</scene> | + | |LIGAND= <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene> |
| - | |ACTIVITY= [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] | + | |ACTIVITY= <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> |
|GENE= MVAS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 Enterococcus faecalis]) | |GENE= MVAS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 Enterococcus faecalis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x9e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x9e OCA], [http://www.ebi.ac.uk/pdbsum/1x9e PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x9e RCSB]</span> | ||
}} | }} | ||
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[[Category: Sutherlin, A.]] | [[Category: Sutherlin, A.]] | ||
[[Category: Vartia, A A.]] | [[Category: Vartia, A A.]] | ||
| - | [[Category: SO4]] | ||
[[Category: thiolase family]] | [[Category: thiolase family]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 00:46:30 2008'' |
Revision as of 21:46, 30 March 2008
| |||||||
| , resolution 2.40Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | MVAS (Enterococcus faecalis) | ||||||
| Activity: | Hydroxymethylglutaryl-CoA synthase, with EC number 2.3.3.10 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Crystal structure of HMG-CoA synthase from Enterococcus faecalis
Overview
Biosynthesis of the isoprenoid precursor, isopentenyl diphosphate, is a critical function in all independently living organisms. There are two major pathways for this synthesis, the non-mevalonate pathway found in most eubacteria and the mevalonate pathway found in animal cells and a number of pathogenic bacteria. An early step in this pathway is the condensation of acetyl-CoA and acetoacetyl-CoA into HMG-CoA, catalyzed by the enzyme HMG-CoA synthase. To explore the possibility of a small molecule inhibitor of the enzyme functioning as a non-cell wall antibiotic, the structure of HMG-CoA synthase from Enterococcus faecalis (MVAS) was determined by selenomethionine MAD phasing to 2.4 A and the enzyme complexed with its second substrate, acetoacetyl-CoA, to 1.9 A. These structures show that HMG-CoA synthase from Enterococcus is a member of the family of thiolase fold enzymes and, while similar to the recently published HMG-CoA synthase structures from Staphylococcus aureus, exhibit significant differences in the structure of the C-terminal domain. The acetoacetyl-CoA binary structure demonstrates reduced coenzyme A and acetoacetate covalently bound to the active site cysteine through a thioester bond. This is consistent with the kinetics of the reaction that have shown acetoacetyl-CoA to be a potent inhibitor of the overall reaction, and provides a starting point in the search for a small molecule inhibitor.
About this Structure
1X9E is a Single protein structure of sequence from Enterococcus faecalis. Full crystallographic information is available from OCA.
Reference
X-ray crystal structures of HMG-CoA synthase from Enterococcus faecalis and a complex with its second substrate/inhibitor acetoacetyl-CoA., Steussy CN, Vartia AA, Burgner JW 2nd, Sutherlin A, Rodwell VW, Stauffacher CV, Biochemistry. 2005 Nov 1;44(43):14256-67. PMID:16245942
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