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Literature summary extracted from

  • Khandekar, S.S.; Gentry, D.R.; Van Aller, G.S.; Warren, P.; Xiang, H.; Silverman, C.; Doyle, M.L.; Chambers, P.A.; Konstantinidis, A.K.; Brandt, M.; Daines, R.A.; Lonsdale, J.T.
    Identification, substrate specificity, and inhibition of the Streptococcus pneumoniae beta-ketoacyl-acyl carrier protein synthase III (FabH) (2001), J. Biol. Chem., 276, 30024-30030.
    View publication on PubMed

Application

EC Number Application Comment Organism
2.3.1.180 pharmacology the enzyme is a target for design and development of antibacterial drugs against pathogenic bacteria Streptococcus pneumoniae

Cloned(Commentary)

EC Number Cloned (Comment) Organism
2.3.1.41 expression as His-tagged protein in Escherichia coli Haemophilus influenzae
2.3.1.41 overexpression of His-tagged FabH in Escherichia coli BL21 (DE3) Streptococcus pneumoniae
2.3.1.180 gene fabH, expression of His-tagged enzyme containing a thrombin cleavage site in strain BL21(DE3) Streptococcus pneumoniae

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.1.41 cerulenin
-
 Escherichia coli
2.3.1.41 cerulenin
-
 Haemophilus influenzae
2.3.1.41 cerulenin
-
 Streptococcus pneumoniae
2.3.1.41 SB418011
-
 Escherichia coli
2.3.1.41 SB418011
-
 Haemophilus influenzae
2.3.1.41 SB418011 strong, synthase III Streptococcus pneumoniae
2.3.1.41 thiolactomycin synthase III Escherichia coli
2.3.1.41 thiolactomycin
-
 Haemophilus influenzae
2.3.1.41 thiolactomycin synthase III; weak Streptococcus pneumoniae
2.3.1.180 cerulenin the IC50 is 0.2 mM Streptococcus pneumoniae
2.3.1.180 SB418011 potent inhibition, the IC50 is 16 nM Streptococcus pneumoniae
2.3.1.180 thiolactomycin weak inhibition, the IC50 is 0.008 mM Streptococcus pneumoniae

KM Value [mM]

EC Number KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
2.3.1.41 0.0186
-
 malonyl-[acyl-carrier protein] synthase III Streptococcus pneumoniae
2.3.1.41 0.0403
-
 acetyl-CoA synthase III Streptococcus pneumoniae
2.3.1.180 0.0186
-
 malonyl-[acyl-carrier protein] pH 7.0, recombinant enzyme Streptococcus pneumoniae
2.3.1.180 0.0403
-
 acetyl-CoA pH 7.0, recombinant enzyme Streptococcus pneumoniae

Molecular Weight [Da]

EC Number Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
2.3.1.41 additional information
-
 amino acid sequence alignment Haemophilus influenzae
2.3.1.41 additional information
-
 amino acid sequence alignment Escherichia coli
2.3.1.41 additional information
-
 amino acid sequence alignment Streptococcus pneumoniae
2.3.1.41 60000
-
 synthase III, gel filtration Streptococcus pneumoniae
2.3.1.180 34000
-
 x * 34000, recombinant detagged enzyme, SDS-PAGE Streptococcus pneumoniae

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.1.180 acetyl-CoA + malonyl-[acyl-carrier protein] Streptococcus pneumoniae
-
 acetoacetyl-[acyl-carrier protein] + CoA + CO2
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
2.3.1.41 Escherichia coli
-
-
-
2.3.1.41 Haemophilus influenzae
-
-
-
2.3.1.41 Streptococcus pneumoniae P0A3C5 synthase III, gene fabH
-
2.3.1.180 Streptococcus pneumoniae P0A3C5 gene fabH
-

Purification (Commentary)

EC Number Purification (Comment) Organism
2.3.1.41 recombinant His-tagged protein from E. coli Haemophilus influenzae
2.3.1.41 recombinant His-tagged synthase III from E. coli Streptococcus pneumoniae
2.3.1.180 recombinant His-tagged enzyme from strain BL21(DE3) by nickel affinity chromatography and gel filtration, the tag is cleaved off by thrombin Streptococcus pneumoniae

Reaction

EC Number Reaction Comment Organism Reaction ID
2.3.1.41 an acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = a 3-oxoacyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein] synthaseIII/FabH: His-Asn-Cys catalytic triad Haemophilus influenzae
a
2.3.1.41 an acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = a 3-oxoacyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein] synthaseIII/FabH: His-Asn-Cys catalytic triad Escherichia coli
a
2.3.1.41 an acyl-[acyl-carrier protein] + a malonyl-[acyl-carrier protein] = a 3-oxoacyl-[acyl-carrier protein] + CO2 + an [acyl-carrier protein] synthaseIII/FabH: His-Asn-Cys catalytic triad Streptococcus pneumoniae
a
2.3.1.180 acetyl-CoA + a malonyl-[acyl-carrier protein] = an acetoacetyl-[acyl-carrier protein] + CoA + CO2 active site structure contains a catalytic triad of His249-Asn279-Cys112 residues Streptococcus pneumoniae
a

Specific Activity [micromol/min/mg]

EC Number Specific Activity Minimum [µmol/min/mg] Specific Activity Maximum [µmol/min/mg] Comment Organism
2.3.1.41 0.005
-
 synthase III Streptococcus pneumoniae
2.3.1.180 additional information
-
 substrate specificity Streptococcus pneumoniae
2.3.1.180 0.005
-
 purified recombinant enzyme, substrates acetyl-CoA and malonyl-[acyl-carrier-protein] Streptococcus pneumoniae

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.1.41 acetyl-CoA + malonyl-[acyl-carrier protein]
-
 Haemophilus influenzae acetoacyl-[acyl-carrier protein] + CO2 + CoA
-
 ?
2.3.1.41 acetyl-CoA + malonyl-[acyl-carrier protein]
-
 Escherichia coli acetoacyl-[acyl-carrier protein] + CO2 + CoA
-
 ?
2.3.1.41 acetyl-CoA + malonyl-[acyl-carrier protein] synthase III, best substrate Streptococcus pneumoniae acetoacyl-[acyl-carrier protein] + CO2 + CoA
-
 ?
2.3.1.41 additional information
-
 Escherichia coli ?
-
 ?
2.3.1.41 additional information synthase III, FabH, has a preference for straight short-chain CoA primers Streptococcus pneumoniae ?
-
 ?
2.3.1.41 saturated acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein] substrate specificity, overview Haemophilus influenzae 3-oxoacyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein]
-
 ?
2.3.1.41 saturated acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein] substrate specificity, overview Escherichia coli 3-oxoacyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein]
-
 ?
2.3.1.41 saturated acyl-[acyl-carrier protein] + malonyl-[acyl-carrier protein] substrate specificity, overview Streptococcus pneumoniae 3-oxoacyl-[acyl-carrier protein] + CO2 + [acyl-carrier protein]
-
 ?
2.3.1.180 acetyl-CoA + malonyl-[acyl-carrier protein]
-
 Streptococcus pneumoniae acetoacetyl-[acyl-carrier protein] + CoA + CO2
-
 ?
2.3.1.180 acetyl-CoA + malonyl-[acyl-carrier protein] preferred CoA primer is acetyl-CoA Streptococcus pneumoniae acetoacetyl-[acyl-carrier protein] + CoA + CO2
-
 ?
2.3.1.180 butyryl-CoA + malonyl-[acyl-carrier protein]
-
 Streptococcus pneumoniae 3-oxo-hexanoyl-[acyl-carrier protein] + CoA + CO2
-
 ?
2.3.1.180 isobutyryl-CoA + malonyl-[acyl-carrier protein]
-
 Streptococcus pneumoniae 3-oxo-4-methyl-pentanoyl-[acyl-carrier protein] + CoA + CO2
-
 ?
2.3.1.180 isovaleryl-CoA + malonyl-[acyl-carrier protein]
-
 Streptococcus pneumoniae 3-oxo-5-methyl-hexanoyl-[acyl-carrier protein] + CoA + CO2
-
 ?
2.3.1.180 additional information substrate specificity, the recombinant enzyme prefers straight short-chain CoA primer substrates, preferred CoA primer is acetyl-CoA, no activity with lauroyl-CoA and palmitoyl-CoA Streptococcus pneumoniae ?
-
 ?

Subunits

EC Number Subunits Comment Organism
2.3.1.180 ? x * 34000, recombinant detagged enzyme, SDS-PAGE Streptococcus pneumoniae

Synonyms

EC Number Synonyms Comment Organism
2.3.1.180 beta-ketoacyl-acyl carrier protein synthase III
-
 Streptococcus pneumoniae
2.3.1.180 FabH
-
 Streptococcus pneumoniae

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
2.3.1.180 7
-
 assay at Streptococcus pneumoniae

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.1.180 0.000016
-
 potent inhibition, the IC50 is 16 nM Streptococcus pneumoniae SB418011
2.3.1.180 0.008
-
 weak inhibition, the IC50 is 0.008 mM Streptococcus pneumoniae thiolactomycin
2.3.1.180 0.2
-
 the IC50 is 0.2 mM Streptococcus pneumoniae cerulenin