Single Turnover of Transient of Reactants Supports a Complex Interplay of Conformational States in the Mode of Action of Mycobacterium tuberculosis Enoyl Reductase
Abstract:The enoyl reductase from Mycobacterium tuberculosis (MtInhA) was shown to be a major target for isoniazid, the most prescribed first-line anti-tuberculosis agent. The MtInhA (EC 1.3.1.9) protein catalyzes the hydride transfer from the 4S hydrogen of β-NADH to carbon-3 of long-chain 2-trans-enoyl thioester substrates (enoyl-ACP or enoyl-CoA) to yield NAD+ and acyl-ACP or acyl-CoA products. The latter are the long carbon chains of the meromycolate branch of mycolic acids, which are high-molecular-weight α-alkyl,… Show more
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