title: Site-directed mutagenesis studies of acetylglutamate synthase delineate the site for the arginine inhibitor.
abstract: N-acetyl-L-glutamate synthase (NAGS), the first enzyme of bacterial/plant arginine biosynthesis and an essential activator of the urea cycle in animals, is, respectively, arginine-inhibited and activated. Site-directed mutagenesis of recombinant Pseudomonas aeruginosa NAGS (PaNAGS) delineates the arginine site in the PaNAGS acetylglutamate kinase-like domain, and, by extension, in human NAGS. Key residues for glutamate binding are identified in the acetyltransferase domain. However, the acetylglutamate kinase-like domain may modulate glutamate binding, since one mutation affecting this domain increases the K(m) for glutamate. The effects on PaNAGS of two mutations found in human NAGS deficiency support the similarity of bacterial and human NAGSs despite their low sequence identity.
authors.affiliation: Instituto de Biomedicina de Valencia (IBV-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Jaime Roig 11, 46010 Valencia, Spain.
authors.forename: Enea
authors.initials: E
authors.lastname: Sancho-Vaello
authors.forename: M Leonor
authors.initials: ML
authors.lastname: Fernández-Murga
authors.forename: Vicente
authors.initials: V
authors.lastname: Rubio
mesh_terms: D000595:Amino Acid Sequence; D051046:Amino-Acid N-Acetyltransferase / Q000737:chemistry* / Q000235:genetics; D001120:Arginine / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D018698:Glutamic Acid / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D011550:Pseudomonas aeruginosa / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry; D016415:Sequence Alignment
chemical_list: D001426:Bacterial Proteins; D011994:Recombinant Proteins; D018698:Glutamic Acid; D001120:Arginine; D051046:Amino-Acid N-Acetyltransferase; C494874:NAGS protein, human