1ysl
From Proteopedia
| Line 1: | Line 1: | ||
[[Image:1ysl.gif|left|200px]] | [[Image:1ysl.gif|left|200px]] | ||
| - | + | <!-- | |
| - | + | The line below this paragraph, containing "STRUCTURE_1ysl", 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_1ysl| PDB=1ysl | SCENE= }} |
| - | + | ||
| - | + | ||
| - | }} | + | |
'''Crystal structure of HMG-CoA synthase from Enterococcus faecalis with AcetoAcetyl-CoA ligand.''' | '''Crystal structure of HMG-CoA synthase from Enterococcus faecalis with AcetoAcetyl-CoA ligand.''' | ||
| Line 32: | Line 29: | ||
[[Category: Sutherlin, A.]] | [[Category: Sutherlin, A.]] | ||
[[Category: Vartia, A A.]] | [[Category: Vartia, A A.]] | ||
| - | [[Category: | + | [[Category: Coenzymea]] |
| - | [[Category: | + | [[Category: Thiolase family]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 16:43:48 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 13:43, 3 May 2008
Crystal structure of HMG-CoA synthase from Enterococcus faecalis with AcetoAcetyl-CoA ligand.
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
1YSL 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 16:43:48 2008
