This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
1x9e
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1x9e.jpg|left|200px]] | [[Image:1x9e.jpg|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1x9e", creates the "Structure Box" on the page. | |
| - | + | You may change the PDB parameter (which sets the PDB file loaded into the applet) | |
| - | + | or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |
| - | + | or leave the SCENE parameter empty for the default display. | |
| - | | | + | --> |
| - | | | + | {{STRUCTURE_1x9e| PDB=1x9e | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal structure of HMG-CoA synthase from Enterococcus faecalis''' | '''Crystal structure of HMG-CoA synthase from Enterococcus faecalis''' | ||
| Line 32: | Line 29: | ||
[[Category: Sutherlin, A.]] | [[Category: Sutherlin, A.]] | ||
[[Category: Vartia, A A.]] | [[Category: Vartia, A A.]] | ||
| - | [[Category: | + | [[Category: Thiolase family]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:44:23 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:44, 3 May 2008
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 Page seeded by OCA on Sat May 3 14:44:23 2008
