title: The N-Acetylglutamate Synthase Family: Structures, Function and Mechanisms.
abstract: 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.
authors.affiliation: Center for Genetic Medicine Research and Department of Integrative Systems Biology, Children's National Medical Center, the George Washington University, Washington, DC 20010, USA. dshi@childrensnational.org.
authors.forename: Dashuang
authors.initials: D
authors.lastname: Shi
authors.affiliation: 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. allewell@umd.edu.
authors.forename: Norma M
authors.initials: NM
authors.lastname: Allewell
authors.affiliation: Center for Genetic Medicine Research and Department of Integrative Systems Biology, Children's National Medical Center, the George Washington University, Washington, DC 20010, USA. mtuchman@childrensnational.org.
authors.forename: Mendel
authors.initials: M
authors.lastname: Tuchman
mesh_terms: D000595:Amino Acid Sequence; D051046:Amino-Acid N-Acetyltransferase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001419:Bacteria / Q000201:enzymology; D020134:Catalytic Domain; D006801:Humans; D008969:Molecular Sequence Data
chemical_list: D051046:Amino-Acid N-Acetyltransferase
keywords: N-acetylglutamate synthase; arginine biosynthesis; catalysis and regulation; crystal structures; urea cycle