beta-ketoacyl-acyl-carrier-protein synthase II
3-oxoacyl-acyl carrier protein synthase I
(Z)-hexadec-11-enoyl-[acyl-carrier-protein]:malonyl-[acyl-carrier-protein] C-acyltransferase (decarboxylating)
This enzyme belongs to thiolase superfamily (see [11] and [12]). This enzyme belongs to the subfamily of type I and type II of beta-ketoacyl-acyl-carrier protein synthase (KAS I & KAS II). This enzyme is KAS II, whereas the counterpart enzyme is KAS I (EC 2.3.1.41; D00824 in EzCatDB), with a similar catalytic site. Moreover, its homologous enzymes, which belong to KAS III subfamily, use acetyl-CoA as primer substrate, instead of acyl-ACP (EC 2.3.1.180; D00825, D00826, D00867 in EzCatDB), unlike KAS I and KAS II. According to the literatre, this enzyme catalyzes the following reactions: (A) Transfer of acyl group from sulfur atom of acyl-ACP to catalytic cysteine (see [15]): (A0) Lys335 modulates the activity of His303 and His340. (A1) His340 (of 1b3n) may act as a general base to deprotonate the nucleophile, Cys163. (Helix dipole moment may also activate the cysteine sidechain.) (A2) The activated thiol group of Cys163 makes a nucleophilic attack on the acyl group of acyl-ACP, leading to a transition-state (I00138). The oxyanion hole, composed of the mainchain amide groups of Cys163 and Phe400, stabilizes the negative charge of the oxyanion on the tetrahedral transition-state (I00138). (A3) His303 may act as a general acid to protonate the leaving sulfur atom of ACP, generating an acyl group on Cys163 (I00139). (B) Hydrolysis of carbon-carbon bond one of which is carboxyl carbon of malonyl-ACP,forming carbanion/enolate transition-state (I00134) (see [7] and [13]): (B0) Lys335 modulates the activity of His303 and His340. (B1) His303 acts as a general base to deprotonate a nearby water molecule to activate it. (B2) The activated water makes a nucleophilic attack on the carboxyl carbon (C3), forming a tetrahedral transition-state (I00140). (B3) The tetrahedral transition-state collapses, to form the carbanion/enolate transition-state (I00134) and to release bicarbonate. Here, His340 acts as a second oxyanion hole, to stabilize the negative charge on the enolate oxygen, which is generated during the formation of the carbanion at the C2 carbon of malonyl group (I00134). (C) Transfer of acyl group from catalytic cysteine to carbanion on the transition-state (I00134): (C0) Protonated His340 stabilizes the enol group of the transition-state (I00134). (C1) The carbanion makes a nucleophilic attack on the acyl group of the intermediate (I00139), forming a tetrahedral transition-state (I00141). The oxyanion of the tetrahedral transition-state (I00141) is stabilized by the oxyanion hole composed of the mainchain amide groups of Cys163 and Phe400. (C2) His340 may act as a general acid to protonate the leaving catalytic residue, Cys163.
Crystal structure of beta-ketoacyl-acyl carrier protein synthase II from E.coli reveals the molecular architecture of condensing enzymes.
The thiolase superfamily: condensing enzymes with diverse reaction specificities.
Roles of the active site water, histidine 303, and phenylalanine 396 in the catalytic mechanism of the elongation condensing enzyme of Streptococcus pneumoniae.
Molecular aspects of beta-ketoacyl synthase (KAS) catalysis.
The 1.8 A crystal structure and active-site architecture of beta-ketoacyl-acyl carrier protein synthase III (FabH) from escherichia coli.
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.
The crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Synechocystis sp. at 1.54 A resolution and its relationship to other condensing enzymes.
Mechanism of the beta-ketoacyl synthase reaction catalyzed by the animal fatty acid synthase.
The 1.3-Angstrom-resolution crystal structure of beta-ketoacyl-acyl carrier protein synthase II from Streptococcus pneumoniae.
The structural biology of type II fatty acid biosynthesis.
Platensimycin is a selective FabF inhibitor with potent antibiotic properties.
Structure of 3-oxoacyl-(acyl-carrier protein) synthase II from Thermus thermophilus HB8.
Acta Crystallogr Sect F Struct Biol Cryst Commun
Divergent evolution of the thiolase superfamily and chalcone synthase family.
Synthesis and biological evaluation of platensimycin analogs.
Isolation, enzyme-bound structure and antibacterial activity of platencin A1 from Streptomyces platensis.
Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.
A template search reveals mechanistic similarities and differences in beta-ketoacyl synthases (KAS) and related enzymes.
[Acyl-carrier protein]-decarboxylated malonyl group (Peptidyl-Ser-phosphopantetheine-S-enolate)
Peptidyl-Cys-tetrahedral-(Z)-hexadec-11-enoyl-[acyl-carrier protein]
[Acyl-carrier protein]-tetrahedral-malonyl group
Peptidyl-Cys-tetrahedral-(Z)-hexadec-11-enoyl-keto-[acyl-carrier protein]
(Z)-hexadec-11-enoyl-[acyl-carrier protein]
(Z)-3-oxooctadec-13-enoyl-[acyl-carrier protein]