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| | {{STRUCTURE_2hdb| PDB=2hdb | SCENE= }} | | {{STRUCTURE_2hdb| PDB=2hdb | SCENE= }} |
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| - | '''HMG-CoA synthase from Enterococcus faecalis. Mutation alanine 110 to glycine'''
| + | ===HMG-CoA synthase from Enterococcus faecalis. Mutation alanine 110 to glycine=== |
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| - | ==Overview==
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| - | Recent structural studies of the HMG-CoA synthase members of the thiolase superfamily have shown that the catalytic loop containing the nucleophilic cysteine follows the phi and psi angle pattern of a II' beta turn. However, the i + 1 residue is conserved as an alanine, which is quite unusual in this position as it must adopt a strained positive phi angle to accommodate the geometry of the turn. To assess the effect of the conserved strain in the catalytic loop, alanine 110 of Enterococcus faecalis 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase was mutated to a glycine. Subsequent enzymatic studies showed that the overall reaction rate of the enzyme was increased 140-fold. An X-ray crystallographic study of the Ala110Gly mutant enzyme demonstrated unanticipated adjustments in the active site that resulted in additional stabilization of all three steps of the reaction pathway. The rates of acetylation and hydrolysis of the mutant enzyme increased because the amide nitrogen of Ser308 shifts 0.4 A toward the catalytic cysteine residue. This motion positions the nitrogen to better stabilize the intermediate negative charge that develops on the carbonyl oxygen of the acetyl group during both the formation of the acyl-enzyme intermediate and its hydrolysis. In addition, the hydroxyl of Ser308 rotates 120 degrees to a position where it is able to stabilize the carbanion intermediate formed by the methyl group of the acetyl-S-enzyme during its condensation with acetoacetyl-CoA.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_17128980}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 17128980 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_17128980}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Synthase]] | | [[Category: Synthase]] |
| | [[Category: Thiolase fold]] | | [[Category: Thiolase fold]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:08:48 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 13:30:55 2008'' |
Revision as of 10:30, 28 July 2008
Template:STRUCTURE 2hdb
HMG-CoA synthase from Enterococcus faecalis. Mutation alanine 110 to glycine
Template:ABSTRACT PUBMED 17128980
About this Structure
2HDB is a Single protein structure of sequence from Enterococcus faecalis. Full crystallographic information is available from OCA.
Reference
A structural limitation on enzyme activity: the case of HMG-CoA synthase., Steussy CN, Robison AD, Tetrick AM, Knight JT, Rodwell VW, Stauffacher CV, Sutherlin AL, Biochemistry. 2006 Dec 5;45(48):14407-14. PMID:17128980
Page seeded by OCA on Mon Jul 28 13:30:55 2008
