Conformational dynamics play important roles upon the function of N-acetylglutamate kinase

Abstract

N-acetylglutamate kinase (NAGK) catalyzes the phosphorylation of N-acetylglutamate. In many bacteria, NAGK catalysis is the rate controlling step in the L-arginine biosynthesis pathway from glutamate to L-arginine and is allosterically inhibited by L-arginine. Many data show that conformational dynamics of NAGKs are essential for their function. The demonstration of the conformational mechanism provides a potential way to improve the yield of arginine. Due to the lack of NAGK catalysis step in arginine synthesis route of mammals, the elucidation of the dynamic mechanism can also provide a way to design a new antivirus drug. This paper reviews how the dynamics affect the activity of NAGKs and are controlled by the effectors. X-ray crystallography and modeling data have shown that in NAGKs, the structural elements required for inhibitor and substrate binding, catalysis and product release, are highly mobile. It is possible to eliminate the inhibition of the arginine and/or block the synthesis of arginine by disturbing the flexibility of the NAGKs. Amino acid kinase family is thought to share some common dynamic features; the flexible structural elements of NAGKs have been identified, but the details of the dynamics and the signal transfer pathways are yet to be elucidated.

Enhancement of himastatin bioproduction via inactivation of atypical repressors in Streptomyces hygroscopicus

“…NAGK catalyzes the controlling step of N -acetyl glutamate phosphorylation and is feedback inhibited by the final product L-Arginine. NAGK thereby serves in large part to regulate the needs of aa biosynthesis against those of aa utilization (Llacer et al, 2007, Yang, 2017). Conserved domain analyses reveal that HmtB contains the conserved acetylglutamate kinase and amino acid kinase family sequence and structure, showing homology with the structure well-identified NAGKs (Fig.…”

Phosphorylation Mechanism of N-Acetyl-l-glutamate Kinase, a QM/MM Study

“…Conformational change of proteins is often observed during substrate binding . Kinases usually exhibit large plasticity that has emerged as the target for development of selective drug therapies. , Conformational dynamics is essential for the function of NAGKs . For E.…”

“…34,35 Conformational dynamics is essential for the function of NAGKs. 36 For E. coli NAGK, the open conformation was suggested to be associated with the substrate entry and product release while the closed conformation is related to catalysis. 18 Here, the conformational change of At-NAGK induced by substrate binding was studied by comparing the MD-simulated structures of NAGK bound with the native substrate NAG and in the absence of the substrate.…”