N-acetyl-L-glutamate kinase (NAGK)

N-acetyl-L-glutamate kinase (NAGK) is a key enzyme in the arginine biosynthetic pathway of microorganisms, fungi, and plants, where it catalyzes the ATP-dependent phosphorylation of N-acetyl-L-glutamate to N-acetyl-L-glutamate-5-phosphate [2, 3, 6]. This enzyme is a member of the amino acid kinase (AAK) family and is essential for the production of ornithine and subsequently arginine in these organisms [12, 23, 31]. Notably, NAGK is absent in mammals, which instead utilize the urea cycle and rely on N-acetylglutamate solely as an allosteric activator of carbamoyl phosphate synthetase 1 [1, 4, 7, 10]. This fundamental difference in metabolism makes NAGK an attractive target for the development of novel antimicrobial and biocidal agents, as its inhibition would selectively disrupt arginine synthesis in pathogens without affecting human metabolic pathways [2, 6, 21, 22, 29, 31]. In many species, NAGK activity is tightly regulated by feedback inhibition from L-arginine, a mechanism that involves complex conformational changes and, in some cases, interaction with the PII signal transduction protein [12, 13, 32, 38]. While no clinical drugs currently target NAGK, structural and mechanistic studies continue to explore its potential for selective inhibition in treating infections caused by pathogens such as Pseudomonas aeruginosa and Mycobacterium tuberculosis [2, 6, 21, 22, 29, 31].

Other names

N-acetylglutamate 5-phosphotransferaseAcetylglutamate phosphokinaseN-acetylglutamate phosphokinaseN-acetylglutamic 5-phosphotransferaseNAGK

Inhibition of the second step of the arginine biosynthetic pathway