Literature summary for 2.3.1.180 extracted from

Nanson, J.D.; Himiari, Z.; Swarbrick, C.M.; Forwood, J.K.
Structural characterisation of the beta-ketoacyl-acyl carrier protein synthases, FabF and FabH, of Yersinia pestis (2015), Sci. Rep., 5, 14797.

Search for more literature for 2.3.1.180

Application

Application	Comment	Organism
drug development	the enzyme is a promising target for the development of therapeutic agents	Yersinia pestis

Cloned(Commentary)

Cloned (Comment)	Organism
gene fabH, recombinant expression of N-terminally His6-tagged enzyme with a TEV protease cleavage site in Escherichia coli strain BL21(DE3) pLysS	Yersinia pestis

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant enzyme in apoform or as acetylated enzyme, hanging drop vapour diffusion technique, mixing of 0.0015 ml of 20 mg/ml protein solution with an equal amount of reservoir solution, containing 10% propan-2-ol, 0.1 M HEPES, pH 7.5, 15% glycerol, 24% PEG 4000, and equilibration against 0.3 ml of reservoir solution, 13°C, acetylated-YpFabH by co-crystallisation with acetyl-CoA at a molar ratio of 5:5:1 of acetyl-CoA-malonyl-CoA-YpFabH at 10 mg/ml protein, X-ray diffraction structure determination and analysis at 18-2.2 A resolution, molecular replacement using the enzyme structure of Escherichia coli, PDB ID 1HN9, as search model	Yersinia pestis

Crystallization (Comment)

Organism

purified recombinant enzyme in apoform or as acetylated enzyme, hanging drop vapour diffusion technique, mixing of 0.0015 ml of 20 mg/ml protein solution with an equal amount of reservoir solution, containing 10% propan-2-ol, 0.1 M HEPES, pH 7.5, 15% glycerol, 24% PEG 4000, and equilibration against 0.3 ml of reservoir solution, 13°C, acetylated-YpFabH by co-crystallisation with acetyl-CoA at a molar ratio of 5:5:1 of acetyl-CoA-malonyl-CoA-YpFabH at 10 mg/ml protein, X-ray diffraction structure determination and analysis at 18-2.2 A resolution, molecular replacement using the enzyme structure of Escherichia coli, PDB ID 1HN9, as search model

Yersinia pestis

Inhibitors

Inhibitors	Comment	Organism
additional information	inhibitor interaction with the active site, structure analysis, docking study, overview. Cerulenin is a poor inhibitor of FabH	Yersinia pestis
platencin	-	Yersinia pestis
platensimycin	-	Yersinia pestis
thiolactomycin	-	Yersinia pestis

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
acetyl-CoA + a malonyl-[acyl-carrier protein]	Yersinia pestis	-	an acetoacetyl-[acyl-carrier protein] + CoA + CO2	-	?

Organism

Organism	UniProt	Comment	Textmining
Yersinia pestis	Q8ZFT7	gene fabH	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant N-terminally His6-tagged enzyme from Escherichia coli strain BL21(DE3) pLysS by nickel affinty chromatography, tag cleavage by TEV protease, gel filtration, and ultrafiltration to over 90% purity	Yersinia pestis

Reaction

Reaction	Comment	Organism	Reaction ID
acetyl-CoA + a malonyl-[acyl-carrier protein] = an acetoacetyl-[acyl-carrier protein] + CoA + CO2	two-stage mechanism, driven by a dipole moment, the active site cysteine, Cys112 in YpFabH attacks the acyl group of a fatty acyl donor, transferring the acyl group to the enzyme. The bound fatty acyl donor molecule is displaced, and the receiving molecule or fatty acyl thioester to be elongated binds, initiating the transfer of the acyl group from the condensing enzyme to the recipient. The remaining residues of the catalytic triad, His243 and Asn273, are thought to stabilise the fatty acyl intermediate during transition states	Yersinia pestis	a

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
acetyl-CoA + a malonyl-[acyl-carrier protein]	-	Yersinia pestis	an acetoacetyl-[acyl-carrier protein] + CoA + CO2	-	?
additional information	enzyme substrate specificity, overview	Yersinia pestis	?	-	?

Subunits

Subunits	Comment	Organism
dimer	the YpFabH monomer contains 10 alpha-helices and 14 beta-strands, the core motif of YpFabH contains a characteristic thiolase fold, monomer interaction analysis, dimer interface structure, and structure comparison with FabF, EC 2.3.1.179	Yersinia pestis

Synonyms

Synonyms	Comment	Organism
beta-ketoacyl-acyl carrier protein synthase III	-	Yersinia pestis
FabH	-	Yersinia pestis

Cofactor

Cofactor	Comment	Organism	Structure
acetyl-CoA	-	Yersinia pestis

General Information

General Information	Comment	Organism
metabolism	the beta-ketoacyl-acyl carrier protein (ACP) synthases, FabB, FabF, and FabH, catalyse the Claisen condensation of fatty acyl-thioesters and malonyl-ACP to form a 3-oxoacyl-ACP intermediate elongated by two carbon atoms. The initial cycle of elongation is catalysed by FabH, involving condensation of malonyl-ACP and acetyl-CoA, while subsequent cycles of elongation are performed by FabB or FabF	Yersinia pestis
additional information	enzyme structure and active site architecture, comparison with FabF, EC 2.3.1.179. Possible substrate and inhibitor interactions of Yersinia pestis FabH, Arg151 of YpFabH clashes with the adenine ring of CoA	Yersinia pestis