1x9e: Difference between revisions
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'''Crystal structure of HMG-CoA synthase from Enterococcus faecalis''' | {{Structure | ||
|PDB= 1x9e |SIZE=350|CAPTION= <scene name='initialview01'>1x9e</scene>, resolution 2.40Å | |||
|SITE= | |||
|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] | |||
|GENE= MVAS ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1351 Enterococcus faecalis]) | |||
}} | |||
'''Crystal structure of HMG-CoA synthase from Enterococcus faecalis''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1X9E is a [ | 1X9E is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Enterococcus_faecalis Enterococcus faecalis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1X9E OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/16245942 16245942] | ||
[[Category: Enterococcus faecalis]] | [[Category: Enterococcus faecalis]] | ||
[[Category: Hydroxymethylglutaryl-CoA synthase]] | [[Category: Hydroxymethylglutaryl-CoA synthase]] | ||
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[[Category: thiolase family]] | [[Category: thiolase family]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 15:06:45 2008'' | ||
Revision as of 13:06, 20 March 2008
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| 1x9e, resolution 2.40Å | |||||||||||||
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| Ligands: | SO4 | ||||||||||||
| Gene: | MVAS (Enterococcus faecalis) | ||||||||||||
| Activity: | Hydroxymethylglutaryl-CoA synthase, with EC number 2.3.3.10 | ||||||||||||
| 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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