UniProt functional annotation for P9WGR1



	UniProt functional annotation for P9WGR1

UniProt codes: P9WGR1, P0A5Y6.

Organism: Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).

Taxonomy: Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.

Function: Enoyl-ACP reductase of the type II fatty acid syntase (FAS- II) system, which is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls (PubMed:25227413). Catalyzes the NADH-dependent reduction of the double bond of 2-trans- enoyl-[acyl-carrier protein], an essential step in the fatty acid elongation cycle of the FAS-II pathway (PubMed:7599116). Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates (PubMed:7599116). The mycobacterial FAS-II system utilizes the products of the FAS-I system as primers to extend fatty acyl chain lengths up to C56, forming the meromycolate chain that serves as the precursor for final mycolic acids (PubMed:25227413). {ECO:0000269|PubMed:7599116, ECO:0000303|PubMed:25227413}.

Function: Is the primary target of the first-line antitubercular drug isoniazid (INH) and of the second-line drug ethionamide (ETH) (PubMed:8284673, PubMed:12406221, PubMed:16906155, PubMed:17227913). Overexpressed inhA confers INH and ETH resistance to M.tuberculosis (PubMed:12406221). The mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of NAD and binding of the INH-NAD adduct to the active site of InhA (PubMed:9417034, PubMed:16906155). Similarly, the ETH-NAD adduct binds InhA (PubMed:17227913). {ECO:0000269|PubMed:12406221, ECO:0000269|PubMed:16906155, ECO:0000269|PubMed:17227913, ECO:0000269|PubMed:9417034, ECO:0000305|PubMed:8284673}.

Catalytic activity: Reaction=a 2,3-saturated acyl-[ACP] + NAD(+) = a (2E)-enoyl-[ACP] + H(+) + NADH; Xref=Rhea:RHEA:10240, Rhea:RHEA-COMP:9925, Rhea:RHEA- COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.9; Evidence={ECO:0000269|PubMed:7599116}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10242; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=a 2,3-saturated acyl-CoA + NAD(+) = a (2E)-enoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:18177, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58856, ChEBI:CHEBI:65111; Evidence={ECO:0000269|PubMed:10521269, ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:21143326, ECO:0000269|PubMed:22987724, ECO:0000269|PubMed:7599116}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18179; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-octenoyl-[ACP] + H(+) + NADH = NAD(+) + octanoyl-[ACP]; Xref=Rhea:RHEA:41528, Rhea:RHEA-COMP:9635, Rhea:RHEA-COMP:9636, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78462, ChEBI:CHEBI:78463; Evidence={ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41529; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-octenoyl-CoA + H(+) + NADH = NAD(+) + octanoyl-CoA; Xref=Rhea:RHEA:63232, ChEBI:CHEBI:15378, ChEBI:CHEBI:57386, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62242; Evidence={ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:22987724, ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63233; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-dodecenoyl-CoA + H(+) + NADH = dodecanoyl-CoA + NAD(+); Xref=Rhea:RHEA:45408, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269|PubMed:10521269, ECO:0000269|PubMed:21143326, ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45409; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-hexadecenoyl-CoA + H(+) + NADH = hexadecanoyl-CoA + NAD(+); Xref=Rhea:RHEA:46072, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:61526; Evidence={ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46073; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-eicosenoyl-CoA + H(+) + NADH = eicosanoyl-CoA + NAD(+); Xref=Rhea:RHEA:46076, ChEBI:CHEBI:15378, ChEBI:CHEBI:57380, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:74691; Evidence={ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46077; Evidence={ECO:0000305|PubMed:7599116};

Catalytic activity: Reaction=(2E)-tetracosenoyl-CoA + H(+) + NADH = NAD(+) + tetracosanoyl- CoA; Xref=Rhea:RHEA:46080, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:65052, ChEBI:CHEBI:74693; Evidence={ECO:0000269|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46081; Evidence={ECO:0000305|PubMed:7599116};

Activity regulation: InhA activity is controlled via phosphorylation: phosphorylation on Thr-266 decreases InhA activity (5-fold reduction) and likely negatively regulates biosynthesis of mycolic acids and growth of the bacterium (PubMed:20864541, PubMed:21143326). The antitubercular pro-drug isoniazid (INH) is oxidatively activated by the catalase-peroxidase KatG and then covalently binds NAD to form an adduct that inhibits the activity of InhA (Ref.5, PubMed:14623976, PubMed:9417034). The inhibitory adduct is the isonicotinic-acyl-NADH where the isonicotinic-acyl group replaces the 4S (and not the 4R) hydrogen of NADH (PubMed:9417034). Similarly, the antitubercular pro- drugs ethionamide (ETH) and prothionamide (PTH) are activated by the flavoprotein monooxygenase EthA, and forms an adduct with NAD (ETH-NAD and PTH-NAD, respectively) that is a tight-binding inhibitor of InhA (PubMed:17227913). Is inhibited by triclosan and derivatives, pyrazole derivative Genz-8575, indole-5-amide Genz-10850, alkyl diphenyl ethers, pyrrolidine carboxamides, arylamides, pyridomycin, methyl-thiazoles, 4- hydroxy-2-pyridones, and N-benzyl-4-((heteroaryl)methyl)benzamides (PubMed:12606558, PubMed:17163639, PubMed:17034137, PubMed:17723305, PubMed:19130456, PubMed:20200152, PubMed:22987724, PubMed:24107081, PubMed:24616444, PubMed:25568071). Pyridomycin shows a unique mode of InhA inhibition by simultaneously blocking parts of the NADH and the lipid substrate-binding pocket of InhA (PubMed:24292073). Is also inhibited by thiadiazole compounds, that have very attractive antitubercular properties (PubMed:27428438). {ECO:0000269|PubMed:12606558, ECO:0000269|PubMed:14623976, ECO:0000269|PubMed:17034137, ECO:0000269|PubMed:17163639, ECO:0000269|PubMed:17227913, ECO:0000269|PubMed:17723305, ECO:0000269|PubMed:19130456, ECO:0000269|PubMed:20200152, ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:22987724, ECO:0000269|PubMed:24107081, ECO:0000269|PubMed:24292073, ECO:0000269|PubMed:24616444, ECO:0000269|PubMed:25568071, ECO:0000269|PubMed:26934341, ECO:0000269|PubMed:27428438, ECO:0000269|PubMed:9417034, ECO:0000269|Ref.5, ECO:0000305|PubMed:21143326}.

Biophysicochemical properties: Kinetic parameters: KM=2.0 uM for 2-trans-octenoyl-ACP (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; KM=8.1 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; KM=66 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:10521269}; KM=19.1 uM for NADH (at pH 6.8) {ECO:0000269|PubMed:20864541}; KM=13.5 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:22987724}; KM=467 uM for 2-trans-octenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; KM=528 uM for 2-trans-octenoyl-CoA (at pH 6.8) {ECO:0000269|PubMed:20864541}; KM=48 uM for 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; KM=27 uM for 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:10521269}; KM=40.9 uM for 2-trans-dodecenoyl-CoA (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:21143326}; KM=1.5 uM for 2-trans-hexadecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; Vmax=2.2 umol/min/mg enzyme for the reduction of 2-trans-octenoyl-ACP (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; Vmax=3.6 umol/min/mg enzyme for the reduction of 2-trans-octenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; Vmax=0.52 umol/min/mg enzyme for the reduction of 2-trans-octenoyl- CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:22987724}; Vmax=15.3 umol/min/mg enzyme for the reduction of 2-trans-octenoyl- CoA (at pH 6.8) {ECO:0000269|PubMed:20864541}; Vmax=5.8 umol/min/mg enzyme for the reduction of 2-trans-dodecenoyl- CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; Vmax=11.4 umol/min/mg enzyme for the reduction of 2-trans-dodecenoyl- CoA (at pH 7.5 and 25 degrees Celsius) {ECO:0000269|PubMed:21143326}; Vmax=4.5 umol/min/mg enzyme for the reduction of 2-trans- hexadecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269|PubMed:7599116}; Note=kcat is 320.4 min(-1) for the reduction of 2-trans-dodecenoyl- CoA (at pH 7.5 and 25 degrees Celsius) (PubMed:21143326). kcat is 278 min(-1) for the reduction of 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) (PubMed:10521269). {ECO:0000269|PubMed:10521269, ECO:0000269|PubMed:21143326};

Pathway: Lipid metabolism; mycolic acid biosynthesis. {ECO:0000303|PubMed:25227413}.

Subunit: Homodimer (PubMed:7599116). Homotetramer (PubMed:10336454, PubMed:16647717). {ECO:0000269|PubMed:10336454, ECO:0000269|PubMed:16647717, ECO:0000269|PubMed:7599116}.

Ptm: Is phosphorylated on Thr-266 in vivo. In vitro, can be phosphorylated by multiple Ser/Thr protein kinases (STPK) such as PknA, PknB, PknE, PknH and PknL. Phosphorylation decreases enzymatic activity. {ECO:0000269|PubMed:20864541, ECO:0000269|PubMed:21143326}.

Miscellaneous: Was identified as a high-confidence drug target. {ECO:0000305|PubMed:19099550}.

Miscellaneous: Many isoniazid- and ethionamide-resistant clinical isolates contain mutations within the inhA locus. Resistance to isoniazid and ethionamide can be conferred by the single substitution of alanine for serine 94; this drug resistance seems to be directly related to a perturbation in the hydrogen-bonding network that decreases the binding of NADH and the INH-NAD adduct. {ECO:0000269|PubMed:16906155, ECO:0000305|PubMed:7886450}.

Similarity: Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
Taxonomy:		Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae; Mycobacterium; Mycobacterium tuberculosis complex.



Function:		Enoyl-ACP reductase of the type II fatty acid syntase (FAS- II) system, which is involved in the biosynthesis of mycolic acids, a major component of mycobacterial cell walls (PubMed:25227413). Catalyzes the NADH-dependent reduction of the double bond of 2-trans- enoyl-[acyl-carrier protein], an essential step in the fatty acid elongation cycle of the FAS-II pathway (PubMed:7599116). Shows preference for long-chain fatty acyl thioester substrates (>C16), and can also use 2-trans-enoyl-CoAs as alternative substrates (PubMed:7599116). The mycobacterial FAS-II system utilizes the products of the FAS-I system as primers to extend fatty acyl chain lengths up to C56, forming the meromycolate chain that serves as the precursor for final mycolic acids (PubMed:25227413). {ECO:0000269\|PubMed:7599116, ECO:0000303\|PubMed:25227413}.



Function:		Is the primary target of the first-line antitubercular drug isoniazid (INH) and of the second-line drug ethionamide (ETH) (PubMed:8284673, PubMed:12406221, PubMed:16906155, PubMed:17227913). Overexpressed inhA confers INH and ETH resistance to M.tuberculosis (PubMed:12406221). The mechanism of isoniazid action against InhA is covalent attachment of the activated form of the drug to the nicotinamide ring of NAD and binding of the INH-NAD adduct to the active site of InhA (PubMed:9417034, PubMed:16906155). Similarly, the ETH-NAD adduct binds InhA (PubMed:17227913). {ECO:0000269\|PubMed:12406221, ECO:0000269\|PubMed:16906155, ECO:0000269\|PubMed:17227913, ECO:0000269\|PubMed:9417034, ECO:0000305\|PubMed:8284673}.


Catalytic activity:		Reaction=a 2,3-saturated acyl-[ACP] + NAD(+) = a (2E)-enoyl-[ACP] + H(+) + NADH; Xref=Rhea:RHEA:10240, Rhea:RHEA-COMP:9925, Rhea:RHEA- COMP:9926, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78784, ChEBI:CHEBI:78785; EC=1.3.1.9; Evidence={ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10242; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=a 2,3-saturated acyl-CoA + NAD(+) = a (2E)-enoyl-CoA + H(+) + NADH; Xref=Rhea:RHEA:18177, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58856, ChEBI:CHEBI:65111; Evidence={ECO:0000269\|PubMed:10521269, ECO:0000269\|PubMed:20864541, ECO:0000269\|PubMed:21143326, ECO:0000269\|PubMed:22987724, ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:18179; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-octenoyl-[ACP] + H(+) + NADH = NAD(+) + octanoyl-[ACP]; Xref=Rhea:RHEA:41528, Rhea:RHEA-COMP:9635, Rhea:RHEA-COMP:9636, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:78462, ChEBI:CHEBI:78463; Evidence={ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41529; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-octenoyl-CoA + H(+) + NADH = NAD(+) + octanoyl-CoA; Xref=Rhea:RHEA:63232, ChEBI:CHEBI:15378, ChEBI:CHEBI:57386, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:62242; Evidence={ECO:0000269\|PubMed:20864541, ECO:0000269\|PubMed:22987724, ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63233; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-dodecenoyl-CoA + H(+) + NADH = dodecanoyl-CoA + NAD(+); Xref=Rhea:RHEA:45408, ChEBI:CHEBI:15378, ChEBI:CHEBI:57330, ChEBI:CHEBI:57375, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; Evidence={ECO:0000269\|PubMed:10521269, ECO:0000269\|PubMed:21143326, ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45409; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-hexadecenoyl-CoA + H(+) + NADH = hexadecanoyl-CoA + NAD(+); Xref=Rhea:RHEA:46072, ChEBI:CHEBI:15378, ChEBI:CHEBI:57379, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:61526; Evidence={ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46073; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-eicosenoyl-CoA + H(+) + NADH = eicosanoyl-CoA + NAD(+); Xref=Rhea:RHEA:46076, ChEBI:CHEBI:15378, ChEBI:CHEBI:57380, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:74691; Evidence={ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46077; Evidence={ECO:0000305\|PubMed:7599116};
Catalytic activity:		Reaction=(2E)-tetracosenoyl-CoA + H(+) + NADH = NAD(+) + tetracosanoyl- CoA; Xref=Rhea:RHEA:46080, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:65052, ChEBI:CHEBI:74693; Evidence={ECO:0000269\|PubMed:7599116}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46081; Evidence={ECO:0000305\|PubMed:7599116};
Activity regulation:		InhA activity is controlled via phosphorylation: phosphorylation on Thr-266 decreases InhA activity (5-fold reduction) and likely negatively regulates biosynthesis of mycolic acids and growth of the bacterium (PubMed:20864541, PubMed:21143326). The antitubercular pro-drug isoniazid (INH) is oxidatively activated by the catalase-peroxidase KatG and then covalently binds NAD to form an adduct that inhibits the activity of InhA (Ref.5, PubMed:14623976, PubMed:9417034). The inhibitory adduct is the isonicotinic-acyl-NADH where the isonicotinic-acyl group replaces the 4S (and not the 4R) hydrogen of NADH (PubMed:9417034). Similarly, the antitubercular pro- drugs ethionamide (ETH) and prothionamide (PTH) are activated by the flavoprotein monooxygenase EthA, and forms an adduct with NAD (ETH-NAD and PTH-NAD, respectively) that is a tight-binding inhibitor of InhA (PubMed:17227913). Is inhibited by triclosan and derivatives, pyrazole derivative Genz-8575, indole-5-amide Genz-10850, alkyl diphenyl ethers, pyrrolidine carboxamides, arylamides, pyridomycin, methyl-thiazoles, 4- hydroxy-2-pyridones, and N-benzyl-4-((heteroaryl)methyl)benzamides (PubMed:12606558, PubMed:17163639, PubMed:17034137, PubMed:17723305, PubMed:19130456, PubMed:20200152, PubMed:22987724, PubMed:24107081, PubMed:24616444, PubMed:25568071). Pyridomycin shows a unique mode of InhA inhibition by simultaneously blocking parts of the NADH and the lipid substrate-binding pocket of InhA (PubMed:24292073). Is also inhibited by thiadiazole compounds, that have very attractive antitubercular properties (PubMed:27428438). {ECO:0000269\|PubMed:12606558, ECO:0000269\|PubMed:14623976, ECO:0000269\|PubMed:17034137, ECO:0000269\|PubMed:17163639, ECO:0000269\|PubMed:17227913, ECO:0000269\|PubMed:17723305, ECO:0000269\|PubMed:19130456, ECO:0000269\|PubMed:20200152, ECO:0000269\|PubMed:20864541, ECO:0000269\|PubMed:22987724, ECO:0000269\|PubMed:24107081, ECO:0000269\|PubMed:24292073, ECO:0000269\|PubMed:24616444, ECO:0000269\|PubMed:25568071, ECO:0000269\|PubMed:26934341, ECO:0000269\|PubMed:27428438, ECO:0000269\|PubMed:9417034, ECO:0000269\|Ref.5, ECO:0000305\|PubMed:21143326}.
Biophysicochemical properties:		Kinetic parameters: KM=2.0 uM for 2-trans-octenoyl-ACP (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; KM=8.1 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; KM=66 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:10521269}; KM=19.1 uM for NADH (at pH 6.8) {ECO:0000269\|PubMed:20864541}; KM=13.5 uM for NADH (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:22987724}; KM=467 uM for 2-trans-octenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; KM=528 uM for 2-trans-octenoyl-CoA (at pH 6.8) {ECO:0000269\|PubMed:20864541}; KM=48 uM for 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; KM=27 uM for 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:10521269}; KM=40.9 uM for 2-trans-dodecenoyl-CoA (at pH 7.5 and 25 degrees Celsius) {ECO:0000269\|PubMed:21143326}; KM=1.5 uM for 2-trans-hexadecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; Vmax=2.2 umol/min/mg enzyme for the reduction of 2-trans-octenoyl-ACP (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; Vmax=3.6 umol/min/mg enzyme for the reduction of 2-trans-octenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; Vmax=0.52 umol/min/mg enzyme for the reduction of 2-trans-octenoyl- CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:22987724}; Vmax=15.3 umol/min/mg enzyme for the reduction of 2-trans-octenoyl- CoA (at pH 6.8) {ECO:0000269\|PubMed:20864541}; Vmax=5.8 umol/min/mg enzyme for the reduction of 2-trans-dodecenoyl- CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; Vmax=11.4 umol/min/mg enzyme for the reduction of 2-trans-dodecenoyl- CoA (at pH 7.5 and 25 degrees Celsius) {ECO:0000269\|PubMed:21143326}; Vmax=4.5 umol/min/mg enzyme for the reduction of 2-trans- hexadecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) {ECO:0000269\|PubMed:7599116}; Note=kcat is 320.4 min(-1) for the reduction of 2-trans-dodecenoyl- CoA (at pH 7.5 and 25 degrees Celsius) (PubMed:21143326). kcat is 278 min(-1) for the reduction of 2-trans-dodecenoyl-CoA (at pH 6.8 and 25 degrees Celsius) (PubMed:10521269). {ECO:0000269\|PubMed:10521269, ECO:0000269\|PubMed:21143326};
Pathway:		Lipid metabolism; mycolic acid biosynthesis. {ECO:0000303\|PubMed:25227413}.
Subunit:		Homodimer (PubMed:7599116). Homotetramer (PubMed:10336454, PubMed:16647717). {ECO:0000269\|PubMed:10336454, ECO:0000269\|PubMed:16647717, ECO:0000269\|PubMed:7599116}.
Ptm:		Is phosphorylated on Thr-266 in vivo. In vitro, can be phosphorylated by multiple Ser/Thr protein kinases (STPK) such as PknA, PknB, PknE, PknH and PknL. Phosphorylation decreases enzymatic activity. {ECO:0000269\|PubMed:20864541, ECO:0000269\|PubMed:21143326}.
Miscellaneous:		Was identified as a high-confidence drug target. {ECO:0000305\|PubMed:19099550}.
Miscellaneous:		Many isoniazid- and ethionamide-resistant clinical isolates contain mutations within the inhA locus. Resistance to isoniazid and ethionamide can be conferred by the single substitution of alanine for serine 94; this drug resistance seems to be directly related to a perturbation in the hydrogen-bonding network that decreases the binding of NADH and the INH-NAD adduct. {ECO:0000269\|PubMed:16906155, ECO:0000305\|PubMed:7886450}.
Similarity:		Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily. {ECO:0000305}.