The N-Acetylglutamate Synthase Family: Structures, Function and Mechanisms

International Journal of Molecular Sciences

Dashuang Shi¹  Norma M. Allewell²  Mendel Tuchman¹ 

[1] Center for Genetic Medicine Research and Department of Integrative Systems Biology, Children’s National Medical Center, the George Washington University, Washington, DC 20010, USA; E-Mail:;Department of Cell Biology and Molecular Genetics and Department of Chemistry and Biochemistry, College of Computer, Mathematical and Natural Sciences, University of Maryland, College Park, MD 20742, USA; E-Mail:

关键词: arginine biosynthesis;    urea cycle;    N-acetylglutamate synthase;    crystal structures;    catalysis and regulation;   

DOI  :  10.3390/ijms160613004

来源: mdpi

【 摘 要 】

N-acetylglutamate synthase (NAGS) catalyzes the production of N-acetylglutamate (NAG) from acetyl-CoA and l-glutamate. In microorganisms and plants, the enzyme functions in the arginine biosynthetic pathway, while in mammals, its major role is to produce the essential co-factor of carbamoyl phosphate synthetase 1 (CPS1) in the urea cycle. Recent work has shown that several different genes encode enzymes that can catalyze NAG formation. A bifunctional enzyme was identified in certain bacteria, which catalyzes both NAGS and N-acetylglutamate kinase (NAGK) activities, the first two steps of the arginine biosynthetic pathway. Interestingly, these bifunctional enzymes have higher sequence similarity to vertebrate NAGS than those of the classical (mono-functional) bacterial NAGS. Solving the structures for both classical bacterial NAGS and bifunctional vertebrate-like NAGS/K has advanced our insight into the regulation and catalytic mechanisms of NAGS, and the evolutionary relationship between the two NAGS groups.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.