This enzyme belongs to chalcone synthase family in thiolase superfamily (see [21]). This enzyme is homologous to the counterpart enzymes from different bacteria (D00826 and D00867 in EzCatDB), with a slightly different catalytic site. Moreover, these enzymes are categorized in type III of beta-ketoacyl-acyl-carrier protein synthases (KAS). According to the literature, the catalysis proceeds through the Ping-Pong reaction mechanism. According to the literature [2], [3], [5], [9], [10], [14], [15] and [21], this enzyme catalyzes the following reactions: (A) Transfer of acyl group from sulfur atom of acetyl-CoA to catalytic cysteine (see [9]): (A0) Asn274 (of 1d9b) modulate the pKa of His244, whereas His244 may lower the pKa of the sidechain of Cys112. (A1) Asp140 acts as a general base to deprotonate the nucleophile, Cys112, through the sidechain of Ser276. (Helix dipole moment may also activate the cysteine sidechain.) (A2) The activated thiol group of Cys112 makes a nucleophilic attack on the acetyl group of acetyl-CoA, leading to a transition-state (I00132). The oxyanion hole, composed of the mainchain amide groups of Cys112 and Gly306, stabilizes the negative charge of the oxyanion on the tetrahedral transition-state (I00132). (A3) His244 acts as a general acid to protonate the leaving sulfur atom of CoA, generating an acetyl group on Cys112 (I00133). (B) Decarboxylation of malonyl-ACP (Elimination of carboxylate group from malonyl group) forming carbanion/enolate transition-state (I00134): (B0) Asn274 and His244 interact with the carbonyl oxygen of the second substrate, malonyl-ACP, and stabilize it. (B1) His244 may act as a general base to deprotonate the carboxylic group of malonyl-ACP, to facilitate the decarboxylation. This reaction generates a carbanion/enolate transition-state (I00134). The enolate is stabilized by Asn274 and His244. (C) Transfer of acetyl group from catalytic cysteine to carbanion on the transition-state (I00134): (C0) Asn274 and His244 stabilize the enol group of the transition-state (I00134). (C1) The carbanion makes a nucleophilic attack on the acetyl group of the acetyl intermediate (I00133), forming a tetrahedral transition-state (I00135). The oxyanion of the tetrahedral transition-state (I00135) is stabilized by the oxyanion hole composed of the mainchain amide groups of Cys112 and Gly306. (C2) Asp140 may act as a general acid to protonate the leaving catalytic residue, Cys112, through the sidechain of Ser276.
Beta-ketoacyl-acyl-carrier-protein synthase III
3-Ketoacyl-acyl carrier protein synthase III
Beta-ketoacyl-acyl carrier protein synthase III
Beta-ketoacyl (acyl carrier protein) synthase III
Beta-ketoacyl-[acyl-carrier-protein] synthase III
Acetyl-CoA:malonyl-[acyl-carrier-protein] C-acyltransferase
[Acyl-carrier protein]-decarboxylated malonyl group (Peptidyl-Ser-phosphopantetheine-S-enolate)
Peptidyl-Cys-tetrahedral-acetyl-keto-[acyl-carrier protein]
Reaction mechanism of recombinant 3-oxoacyl-(acyl-carrier-protein) synthase III from Cuphea wrightii embryo, a fatty acid synthase type II condensing enzyme.
Mechanism of chalcone synthase. pKa of the catalytic cysteine and the role of the conserved histidine in a plant polyketide synthase.
beta-Ketoacyl-[acyl carrier protein] synthase I of Escherichia coli: aspects of the condensation mechanism revealed by analyses of mutations in the active site pocket.
Crystal structure of the priming beta-ketosynthase from the R1128 polyketide biosynthetic pathway.
First X-ray cocrystal structure of a bacterial FabH condensing enzyme and a small molecule inhibitor achieved using rational design and homology modeling.
Probing the mechanism of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III mtFabH: factors influencing catalysis and substrate specificity.
Crystal structure of a substrate complex of Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III (FabH) with lauroyl-coenzyme A.
Crystal structure and substrate specificity of the beta-ketoacyl-acyl carrier protein synthase III (FabH) from Staphylococcus aureus.
Probing reactivity and substrate specificity of both subunits of the dimeric Mycobacterium tuberculosis FabH using alkyl-CoA disulfide inhibitors and acyl-CoA substrates.
Crystal structures of bacterial FabH suggest a molecular basis for the substrate specificity of the enzyme.
The X-ray crystal structure of beta-ketoacyl [acyl carrier protein] synthase I.
Crystal structure of beta-ketoacyl-acyl carrier protein synthase III. A key condensing enzyme in bacterial fatty acid biosynthesis.
The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli.
Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl carrier protein synthase III.
Identification and analysis of the acyl carrier protein (ACP) docking site on beta-ketoacyl-ACP synthase III.
Refined structures of beta-ketoacyl-acyl carrier protein synthase III.
A template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes.
The structural biology of type II fatty acid biosynthesis.
The thiolase superfamily: condensing enzymes with diverse reaction specificities.
Alkyl-CoA disulfides as inhibitors and mechanistic probes for FabH enzymes.
Separate entrance and exit portals for ligand traffic in Mycobacterium tuberculosis FabH.
Divergent evolution of the thiolase superfamily and chalcone synthase family.