2hdb
From Proteopedia
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|PDB= 2hdb |SIZE=350|CAPTION= <scene name='initialview01'>2hdb</scene>, resolution 2.20Å | |PDB= 2hdb |SIZE=350|CAPTION= <scene name='initialview01'>2hdb</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand= | + | |LIGAND= <scene name='pdbligand=MES:2-(N-MORPHOLINO)-ETHANESULFONIC+ACID'>MES</scene>, <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=[[1ysl|1YSL]], [[1x9e|1X9E]], [[1txt|1TXT]], [[1tvz|1TVZ]], [[1xpk|1XPK]], [[1xpm|1XPM]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2hdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2hdb OCA], [http://www.ebi.ac.uk/pdbsum/2hdb PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2hdb RCSB]</span> | ||
}} | }} | ||
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[[Category: Steussy, C N.]] | [[Category: Steussy, C N.]] | ||
[[Category: Sutherlin, A.]] | [[Category: Sutherlin, A.]] | ||
| - | [[Category: MES]] | ||
| - | [[Category: SO4]] | ||
[[Category: mutant]] | [[Category: mutant]] | ||
[[Category: protein]] | [[Category: protein]] | ||
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[[Category: thiolase fold]] | [[Category: thiolase fold]] | ||
| - | ''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 03:28:51 2008'' |
Revision as of 00:28, 31 March 2008
| |||||||
| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | mvaS (Enterococcus faecalis) | ||||||
| Activity: | Hydroxymethylglutaryl-CoA synthase, with EC number 2.3.3.10 | ||||||
| Related: | 1YSL, 1X9E, 1TXT, 1TVZ, 1XPK, 1XPM
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
HMG-CoA synthase from Enterococcus faecalis. Mutation alanine 110 to glycine
Overview
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.
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
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