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). 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). a 2,3-saturated acyl-[ACP] + NAD(+) = a (2E)-enoyl-[ACP] + H(+) + NADH a 2,3-saturated acyl-CoA + NAD(+) = a (2E)-enoyl-CoA + H(+) + NADH (2E)-octenoyl-[ACP] + H(+) + NADH = NAD(+) + octanoyl-[ACP] (2E)-octenoyl-CoA + H(+) + NADH = NAD(+) + octanoyl-CoA (2E)-dodecenoyl-CoA + H(+) + NADH = dodecanoyl-CoA + NAD(+) (2E)-hexadecenoyl-CoA + H(+) + NADH = hexadecanoyl-CoA + NAD(+) (2E)-eicosenoyl-CoA + H(+) + NADH = eicosanoyl-CoA + NAD(+) (2E)-tetracosenoyl-CoA + H(+) + NADH = NAD(+) + tetracosanoyl-CoA 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). 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). Lipid metabolism; mycolic acid biosynthesis. Homodimer (PubMed:7599116). Homotetramer (PubMed:10336454, PubMed:16647717). 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. Was identified as a high-confidence drug target. 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. Belongs to the short-chain dehydrogenases/reductases (SDR) family. FabI subfamily.