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Literature summary for 1.3.1.9 extracted from

  • Parikh, S.; Xiao, G.; Tonge, P.
    Inhibition of InhA, the enoyl reductase from Mycobacterium tuberculosis, by triclosan and isoniazid (2000), Biochemistry, 39, 7645-7650 .
    View publication on PubMed
Search for more literature for 1.3.1.9

Application

Application Comment Organism
pharmacology the enzyme is a target for the antitubercular drug isoniazid. InhA inhibitors targeted at the enoyl substrate binding site may be effective against existing isoniazid-resistant strains of Mycobacterium tuberculosis Mycobacterium tuberculosis

Protein Variants

Protein Variants Comment Organism
A124V mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan Mycolicibacterium smegmatis
I21V InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant Mycobacterium tuberculosis
I47T InhA mutation that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constant Mycobacterium tuberculosis
M161V mutantion results in resistance of Mycobacterium smegmatis to triclosan and significantly reduced affinity of the enzyme for triclosan Mycolicibacterium smegmatis
Y158F mutation reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition Mycobacterium tuberculosis

Inhibitors

Inhibitors Comment Organism Structure
isoniazid
-
 Mycobacterium tuberculosis
isoniazid
-
 Mycolicibacterium smegmatis
triclosan binding of triclosan to wild-type InhA is uncompetitive with respect to both NADH and trans-2-dodecenoyl-CoA. Replacement of Y158, the catalytic tyrosine residue, with Phe, reduces the affinity of triclosan for the enzyme and results in noncompetitive inhibition. I47T and I21V, two InhA mutations that occur in isoniazid-resistant clinical isolates of Mycobacterium tuberculosis, show unimpaired inhibition by triclosan, with uncompetitive inhibition constants Mycobacterium tuberculosis
triclosan
-
 Mycolicibacterium smegmatis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.002
-
 NADH pH 6.8, 25°C, mutant enzyme Y158F Mycobacterium tuberculosis
0.01
-
 trans-2-hexadecenoyl-CoA pH 6.8, 25°C, mutant enzyme M161V Mycolicibacterium smegmatis
0.036
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I47T Mycobacterium tuberculosis
0.046
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, wild-type enzyme Mycobacterium tuberculosis
0.066
-
 NADH pH 6.8, 25°C, wild-type enzyme Mycobacterium tuberculosis
0.07
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I21V Mycobacterium tuberculosis
0.07
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme Y158F Mycobacterium tuberculosis
0.072
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme A124V Mycolicibacterium smegmatis
0.104
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme S94A Mycobacterium tuberculosis
0.12
-
 NADH pH 6.8, 25°C, mutant enzyme I21V Mycobacterium tuberculosis
0.142
-
 NADH pH 6.8, 25°C, mutant enzyme A124V Mycolicibacterium smegmatis
0.152
-
 NADH pH 6.8, 25°C, mutant enzyme I47T Mycobacterium tuberculosis
0.25
-
 NADH pH 6.8, 25°C, mutant enzyme S94A Mycobacterium tuberculosis
0.332
-
 trans-2-hexadecenoyl-CoA pH 6.8, 25°C, mutant enzyme M161V Mycolicibacterium smegmatis

Organism

Organism UniProt Comment Textmining
Mycobacterium tuberculosis P9WGR1
-
-
Mycobacterium tuberculosis ATCC 25618 P9WGR1
-
-
Mycolicibacterium smegmatis P42829
-
-
Mycolicibacterium smegmatis ATCC 700084 P42829
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
trans-2-dodecenoyl-CoA + NADH + H+
-
 Mycobacterium tuberculosis dodecanoyl-CoA + NAD+
-
 ?
trans-2-dodecenoyl-CoA + NADH + H+
-
 Mycolicibacterium smegmatis dodecanoyl-CoA + NAD+
-
 ?
trans-2-dodecenoyl-CoA + NADH + H+
-
 Mycolicibacterium smegmatis ATCC 700084 dodecanoyl-CoA + NAD+
-
 ?
trans-2-dodecenoyl-CoA + NADH + H+
-
 Mycobacterium tuberculosis ATCC 25618 dodecanoyl-CoA + NAD+
-
 ?
trans-2-hexadecenoyl-CoA + NADH + H+
-
 Mycobacterium tuberculosis hexadecanoyl-CoA + NAD+
-
 ?
trans-2-hexadecenoyl-CoA + NADH + H+
-
 Mycolicibacterium smegmatis hexadecanoyl-CoA + NAD+
-
 ?
trans-2-hexadecenoyl-CoA + NADH + H+
-
 Mycolicibacterium smegmatis ATCC 700084 hexadecanoyl-CoA + NAD+
-
 ?
trans-2-hexadecenoyl-CoA + NADH + H+
-
 Mycobacterium tuberculosis ATCC 25618 hexadecanoyl-CoA + NAD+
-
 ?

Synonyms

Synonyms Comment Organism
InhA
-
 Mycobacterium tuberculosis
InhA
-
 Mycolicibacterium smegmatis

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
25
-
 assay at Mycobacterium tuberculosis
25
-
 assay at Mycolicibacterium smegmatis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
0.35
-
 NADH pH 6.8, 25°C, mutant enzyme Y158F Mycobacterium tuberculosis
0.35
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme Y158F Mycobacterium tuberculosis
8.35
-
 NADH pH 6.8, 25°C, wild-type enzyme Mycobacterium tuberculosis
8.35
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, wild-type enzyme Mycobacterium tuberculosis
11.7
-
 trans-2-hexadecenoyl-CoA pH 6.8, 25°C, mutant enzyme M161V Mycolicibacterium smegmatis
12
-
 NADH pH 6.8, 25°C, mutant enzyme I47T Mycobacterium tuberculosis
12
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I47T Mycobacterium tuberculosis
14.35
-
 NADH pH 6.8, 25°C, mutant enzyme A124V Mycolicibacterium smegmatis
14.35
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme A124V Mycolicibacterium smegmatis
15.4
-
 NADH pH 6.8, 25°C, mutant enzyme I21V Mycobacterium tuberculosis
15.4
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I21V Mycobacterium tuberculosis
16.55
-
 NADH pH 6.8, 25°C, mutant enzyme S94A Mycobacterium tuberculosis
16.55
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme S94A Mycobacterium tuberculosis

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.8
-
 assay at Mycobacterium tuberculosis
6.8
-
 assay at Mycolicibacterium smegmatis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.0044
-
 triclosan mutant enzyme M161V, pH 6.8, 25°C Mycolicibacterium smegmatis
0.036
-
 triclosan mutant enzyme Y158F, pH 6.8, 25°C Mycobacterium tuberculosis

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
5
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme Y158F Mycobacterium tuberculosis
148.3
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme S94A Mycobacterium tuberculosis
181.52
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, wild-type enzyme Mycobacterium tuberculosis
198.3
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme A124V Mycolicibacterium smegmatis
220
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I21V Mycobacterium tuberculosis
333.3
-
 trans-2-dodecenoyl-CoA pH 6.8, 25°C, mutant enzyme I47T Mycobacterium tuberculosis
1166.7
-
 trans-2-hexadecenoyl-CoA pH 6.8, 25°C, mutant enzyme M161V Mycolicibacterium smegmatis