Aspartate decarboxylase PanD (PanD)

Aspartate decarboxylase PanD is an essential enzyme in *Mycobacterium tuberculosis* responsible for the decarboxylation of L-aspartate to β-alanine, a critical step in the biosynthesis of coenzyme A. Pyrazinoic acid, the active metabolite of the anti-tuberculosis prodrug pyrazinamide, exerts its bactericidal effect by binding to PanD and inducing its degradation by the mycobacterial ClpC1–ClpP protease complex, leading to disruption of coenzyme A biosynthesis and subsequent bacterial death. Additionally, pyrazinoic acid acts as a protonophore, dissipating the proton motive force and disturbing cellular energetics, contributing to its killing effect. Resistance arises from mutations in panD or in the activating enzyme pyrazinamidase (pncA)[1][3][5][6][7][8][9].

Other names

PanDaspartate decarboxylase (Mycobacterium tuberculosis)MTb PanD

Pyrazinamide is a prodrug converted by mycobacterial pyrazinamidase to pyrazinoic acid, which binds to and disrupts PanD, leading to its degradation and inhibition of coenzyme A biosynthesis[1][3][5][9]. Pyrazinoic acid also acts as a protonophore, disrupting membrane energetics and proton motive force, which impairs cellular metabolism[6][7][8].