Multifunctional NadC homologue (PyrZ) (PyrZ)

PyrZ is a multifunctional enzyme and a homologue of NadC (quinolinic acid phosphoribosyltransferase), recently identified and characterized as a central component of the biosynthetic gene cluster for pyridomycin, a potent antimycobacterial natural product [1, 2]. Unlike typical NadC enzymes that primarily catalyze the formation of nicotinic acid mononucleotide (NAMN), PyrZ is unique for its bifunctional or multifunctional capability, facilitating the conversion of quinolinic acid into nicotinic acid through successive steps of formation, dephosphorylation, and ribose hydrolysis [1, 3]. Because NadC is a clinically validated therapeutic target in Mycobacterium tuberculosis, the structural and mechanistic characterization of PyrZ provides a critical model for understanding alternative NAD metabolic pathways in pathogens [2, 11]. Small-molecule inhibitors, such as the anti-tuberculosis drug pyrazinamide, have shown activity against homologues of this enzyme, making it a focal point for the development of novel antitubercular agents [1, 5]. Targeting this enzyme offers a strategy to combat drug-resistant tuberculosis by disrupting an essential metabolic process that supports bacterial survival and replication [11].

Other names

pyrZMultifunctional NadC-like proteinBifunctional NadC homologueNadC homologueQuinolinic acid phosphoribosyltransferase homologue

Inhibition of the enzymatic activity of the NadC homologue disrupts the de novo biosynthesis of nicotinamide adenine dinucleotide (NAD), leading to metabolic failure and bacterial cell death.