Mycobacterial NADH dehydrogenase-2 (NDH-2) (NDH-2)

Mycobacterial NADH dehydrogenase-2 (NDH-2) is a vital respiratory enzyme in Mycobacterium tuberculosis that serves as a primary entry point for electrons into the electron transport chain [1, 2]. It catalyzes the oxidation of NADH to NAD+ and the concomitant reduction of menaquinone, a process essential for maintaining cellular redox homeostasis and driving oxidative phosphorylation [2, 6]. Unlike the multi-subunit Type I NADH dehydrogenase (NDH-1), NDH-2 is a single-subunit, non-electrogenic enzyme that does not pump protons across the membrane [1, 3]. Because NDH-2 is absent in humans, it is considered a high-priority target for the development of new tuberculosis treatments with reduced host toxicity [1, 5]. Inhibitors of NDH-2, such as phenothiazines and various experimental small molecules like quinolinyl pyrimidines, disrupt the bacterial energy supply and redox balance, leading to growth inhibition and cell death [1, 8]. Recent structural studies have further elucidated its dimeric nature and binding sites, facilitating the design of more potent and selective antimycobacterial agents [3, 9].

Other names

Type II NADH dehydrogenaseNADH:menaquinone oxidoreductase (non-electrogenic)ndhndhA

Inhibition of NADH oxidation and electron transfer to menaquinone, leading to disruption of the respiratory chain and ATP synthesis.