Malate dehydrogenase (bacterial) (MDH) (MDH)

Bacterial malate dehydrogenase (MDH) is a vital enzyme in the tricarboxylic acid (TCA) cycle, catalyzing the reversible oxidation of L-malate to oxaloacetate with the reduction of NAD+ to NADH (PMID: 25613731). This enzyme is essential for energy production, gluconeogenesis, and maintaining the redox balance within bacterial cells, making it a critical component for the survival and pathogenesis of various bacteria, including Mycobacterium tuberculosis and Burkholderia pseudomallei (PMID: 30243825). As a therapeutic target, bacterial MDH is attractive because its inhibition leads to a collapse of central metabolism and a significant reduction in cellular ATP levels. While MDH is conserved across all domains of life, significant structural differences exist between bacterial versions and human mitochondrial (MDH2) or cytosolic (MDH1) isoforms, allowing for the development of selective inhibitors (PMID: 28434863). Current drug discovery efforts focus on identifying small molecules, such as certain polyphenols and synthetic sulfonamides, that can selectively bind to the bacterial enzyme's active or allosteric sites (PMID: 21859113). Successfully targeting this enzyme could provide a new mechanism for treating multi-drug resistant bacterial infections by disrupting fundamental metabolic pathways.

Other names

L-malate dehydrogenaseMalic dehydrogenase(S)-malate:NAD+ oxidoreductase

Inhibition of the catalytic activity of malate dehydrogenase, disrupting the tricarboxylic acid (TCA) cycle and cellular respiration.