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EC Number

Catalytic Site Atlas

CSA LITERATURE entry for 1afw

E.C. nameacetyl-CoA C-acyltransferase
SpeciesSaccharomyces cerevisiae (Baker's yeast)
E.C. Number (IntEnz)
CSA Homologues of 1afwThere are 36 Homologs
CSA Entries With UniProtID P27796
CSA Entries With EC Number
PDBe Entry 1afw
PDBSum Entry 1afw
MACiE Entry M0077

Literature Report

IntroductionThiolases form a ubiquitous family of enzymes found in both prokaryotes and eukaryotes. Thiolases catalyse the reversible two step cleavage of 3-ketoacyl-CoA into acyl-CoA and acetyl-CoA. There are two classes of thiolases, I and II. This is a Class II thiolase. Class II only acts upon acetoacetyl-CoA and its main function is to synthesise this compound in a Claisen condensation reaction important in several biosynthetic pathways.
MechansimHis375 deprotonates Cys125 to activate it as a nucleophile. Cys125 attacks the carbonyl of the acyl-CoA in an addition reaction, forming an oxyanion transition state. This is stabilised by the main-chain amide of Gly405. The oxyanion collapses, eliminating CoA with concomitant deprotonation of Cys403. Cys403 then deprotonates the methyl group of the acetyl CoA with concomitant double bond rearrangement. The acetyl-CoA oxyanion collapses, initiating a nucleophilic attack on the acylated Cys125 in an addition reaction. The oxyanion collapses eliminating Cys125 with concomitant deprotonation of His375, restoring the enzyme to its native state.

Catalytic Sites for 1afw

Annotated By Reference To The Literature - Site 1 (Perform Site Search)
ResidueChainNumberUniProtKB NumberFunctional PartFunctionTargetDescription
CysA125125macie:sideChainDeprotonated cysteine is the nucleophile in both the forward and reverse forms of this reaction. It is acylated by the substrate, and remains covalently bound throughout the reaction.
HisA375375macie:sideChainDeprotonates Cys125 to activate it as a nucleophile. May also stabilise the negatively charged transition state, when in the positively charged protonated state.
CysA403403macie:sideChainDonates a proton to the leaving group.
GlyA405405macie:mainChainAmideStabilises the oxyanion transition states.

Literature References

Modis Y
Crystallographic analysis of the reaction pathway of Zoogloea ramigera biosynthetic thiolase.
J Mol Biol 2000 297 1171-1182
PubMed: 10764581
Mathieu M
The 1.8 A crystal structure of the dimeric peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: implications for substrate binding and reaction mechanism.
J Mol Biol 1997 273 714-728
PubMed: 9402066