Ammonia-dependent NAD synthetase (NadE)

Ammonia-dependent NAD synthetase, commonly referred to as NadE, is a critical enzyme that catalyzes the final step in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). This enzyme facilitates the ATP-dependent amidation of nicotinic acid adenine dinucleotide (NaAD) using ammonia as the nitrogen donor. It is essential for the survival of various bacterial pathogens, including Mycobacterium tuberculosis and Staphylococcus aureus, as NAD+ is a vital cofactor for numerous metabolic and regulatory processes. Because many bacteria rely on this ammonia-dependent form while humans utilize a glutamine-dependent version (NADSYN1), NadE is a promising target for the development of selective antibacterial agents. Inhibiting NadE disrupts the cellular energy balance and redox homeostasis, making it a potent focal point for treating multi-drug resistant infections.

Other names

NH3-dependent NAD synthetaseNAD+ synthase (ammonia-dependent)NadEDeamido-NAD+ amido-ligase (AMP-forming)Nicotinamide adenine dinucleotide synthetase

Inhibition of the ATP-dependent amidation of nicotinic acid adenine dinucleotide (NaAD) to nicotinamide adenine dinucleotide (NAD+), leading to depletion of essential NAD+ levels and bacterial cell death.