title: Effect of arginine on oligomerization and stability of N-acetylglutamate synthase.
abstract: N-acetylglutamate synthase (NAGS; E.C.2.3.1.1) catalyzes the formation of N-acetylglutamate (NAG) from acetyl coenzyme A and glutamate. In microorganisms and plants, NAG is the first intermediate of the L-arginine biosynthesis; in animals, NAG is an allosteric activator of carbamylphosphate synthetase I and III. In some bacteria bifunctional N-acetylglutamate synthase-kinase (NAGS-K) catalyzes the first two steps of L-arginine biosynthesis. L-arginine inhibits NAGS in bacteria, fungi, and plants and activates NAGS in mammals. L-arginine increased thermal stability of the NAGS-K from Maricaulis maris (MmNAGS-K) while it destabilized the NAGS-K from Xanthomonas campestris (XcNAGS-K). Analytical gel chromatography and ultracentrifugation indicated tetrameric structure of the MmMNAGS-K in the presence and absence of L-arginine and a tetramer-octamer equilibrium that shifted towards tetramers upon binding of L-arginine for the XcNAGS-K. Analytical gel chromatography of mouse NAGS (mNAGS) indicated either different oligomerization states that are in moderate to slow exchange with each other or deviation from the spherical shape of the mNAGS protein. The partition coefficient of the mNAGS increased in the presence of L-arginine suggesting smaller hydrodynamic radius due to change in either conformation or oligomerization. Different effects of L-arginine on oligomerization of NAGS may have implications for efforts to determine the three-dimensional structure of mammalian NAGS.
authors.affiliation: Center for Genetic Medicine Research; Children's National Medical Center, Washington, DC, USA.
authors.forename: N
authors.initials: N
authors.lastname: Haskins
authors.affiliation: American Academy of Otolaryngology - Head and Neck Surgery Foundation, Alexandria VA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Mumo
authors.affiliation: National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, USA.
authors.forename: P H
authors.initials: PH
authors.lastname: Brown
authors.affiliation: Center for Genetic Medicine Research; Children's National Medical Center, Washington, DC, USA.
authors.forename: M
authors.initials: M
authors.lastname: Tuchman
authors.affiliation: Center for Genetic Medicine Research; Children's National Medical Center, Washington, DC, USA.
authors.forename: H
authors.initials: H
authors.lastname: Morizono
authors.affiliation: Center for Genetic Medicine Research; Children's National Medical Center, Washington, DC, USA.
authors.forename: L
authors.initials: L
authors.lastname: Caldovic
mesh_terms: D020561:Alphaproteobacteria / Q000201:enzymology*; D051046:Amino-Acid N-Acetyltransferase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D001120:Arginine / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D016959:Xanthomonas campestris / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D001120:Arginine; D051046:Amino-Acid N-Acetyltransferase; C494877:Nags protein, mouse