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Literature summary extracted from

  • Luckner, S.R.; Liu, N.; am Ende, C.W.; Tonge, P.J.; Kisker, C.
    A slow, tight binding inhibitor of InhA, the enoyl-acyl carrier protein reductase from Mycobacterium tuberculosis (2010), J. Biol. Chem., 285, 14330-14337.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.3.1.9 drug development InhA is an attractive target for the development of drugs against tuberculosis Mycobacterium tuberculosis

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.3.1.9 expression of His-tagged InhA in Escherichia coli BL21(DE3) Mycobacterium tuberculosis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.3.1.9 purified recombinant His-tagged InhA in a ternary complex with NAD+ and PT70, 10 mg/ml protein is combined with NAD and PT70 in a molar ratio of 1:5:200, mixing of euqual volumes of protein and reservoir solution, the latter containing 12-16% w/v PEG 4000, 1% DMSO, 100 mM N-(2-acetamido)iminodiacetic acid, pH 6.8, and 100-250 mM ammonium acetate, 22°C, 4 days, X-ray diffraction structure determination and analysis at 1.8-2.1 A resolution, modelling, overview Mycobacterium tuberculosis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.3.1.9 2-(o-tolyloxy)-5-hexylphenol i.e. PT70, a slow, tight binding inhibitor of InhA. PT70 binds preferentially to the InhA-NAD+ complex, binding structure, overview. It has a residence time of 24 min on the target, which is 14000times longer than that of the rapid reversible inhibitor from which it is derived. The slow onset inhibition is coupled to ordering of an active site loop, which leads to the closure of the substrate-binding pocke Mycobacterium tuberculosis

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.3.1.9 an acyl-[acyl-carrier protein] + NAD+ Mycobacterium tuberculosis
-
 a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
 ?
1.3.1.9 an acyl-[acyl-carrier protein] + NAD+ Mycobacterium tuberculosis H37Rv
-
 a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.3.1.9 Mycobacterium tuberculosis P9WGR1
-
-
1.3.1.9 Mycobacterium tuberculosis H37Rv P9WGR1
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.3.1.9 recombinant His-tagged InhA from Escherichia coli BL21(DE3) by nickel affinity chromatography and gel filtration Mycobacterium tuberculosis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.3.1.9 an acyl-[acyl-carrier protein] + NAD+
-
 Mycobacterium tuberculosis a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
 ?
1.3.1.9 an acyl-[acyl-carrier protein] + NAD+
-
 Mycobacterium tuberculosis H37Rv a trans-2,3-dehydroacyl-[acyl-carrier protein] + NADH + H+
-
 ?
1.3.1.9 additional information activity detection using trans-2-dodecenyl-CoA and NADH as substrate and cofactor Mycobacterium tuberculosis ?
-
 ?
1.3.1.9 additional information activity detection using trans-2-dodecenyl-CoA and NADH as substrate and cofactor Mycobacterium tuberculosis H37Rv ?
-
 ?

Synonyms

EC Number Synonyms Comment Organism
1.3.1.9 enoyl-ACP reductase
-
 Mycobacterium tuberculosis
1.3.1.9 InhA
-
 Mycobacterium tuberculosis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.3.1.9 6.8
-
 assay at Mycobacterium tuberculosis

Cofactor

EC Number Cofactor Comment Organism Structure
1.3.1.9 NAD+ binding structure, overview Mycobacterium tuberculosis

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
1.3.1.9 additional information
-
 additional information inhibition kinetics, overview Mycobacterium tuberculosis
1.3.1.9 0.000000022
-
 2-(o-tolyloxy)-5-hexylphenol pH 6.8, temperature not specified in the publication Mycobacterium tuberculosis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.3.1.9 0.0000053
-
 pH 6.8, temperature not specified in the publication Mycobacterium tuberculosis 2-(o-tolyloxy)-5-hexylphenol