Biomaterial Database

Mechanism of arginine regulation of acetylglutamate synthase, the first enzyme of arginine synthesis. 2009

Enea Sancho-Vaello, and María L Fernández-Murga, and Vicente Rubio

Instituto de Biomedicina de Valencia (IBV-CSIC), Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER-ISCIII), Valencia, Spain.

N-acetyl-L-glutamate synthase (NAGS), the first enzyme of arginine biosynthesis in bacteria/plants and an essential urea cycle activator in animals, is, respectively, arginine-inhibited and activated. Arginine binds to the hexameric ring-forming amino acid kinase (AAK) domain of NAGS. We show that arginine inhibits Pseudomonas aeruginosa NAGS by altering the functions of the distant, substrate binding/catalytic GCN5-related N-acetyltransferase (GNAT) domain, increasing K(m)(Glu), decreasing V(max) and triggering substrate inhibition by AcCoA. These effects involve centrally the interdomain linker, since we show that linker elongation or two-residue linker shortening hampers and mimics, respectively, arginine inhibition. We propose a regulatory mechanism in which arginine triggers the expansion of the hexameric NAGS ring, altering AAK-GNAT domain interactions, and the modulation by these interactions of GNAT domain functions, explaining arginine regulation.

UI	MeSH Term	Description	Entries
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D011550	Pseudomonas aeruginosa	A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.	Bacillus aeruginosus,Bacillus pyocyaneus,Bacterium aeruginosum,Bacterium pyocyaneum,Micrococcus pyocyaneus,Pseudomonas polycolor,Pseudomonas pyocyanea
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D001120	Arginine	An essential amino acid that is physiologically active in the L-form.	Arginine Hydrochloride,Arginine, L-Isomer,DL-Arginine Acetate, Monohydrate,L-Arginine,Arginine, L Isomer,DL Arginine Acetate, Monohydrate,Hydrochloride, Arginine,L Arginine,L-Isomer Arginine,Monohydrate DL-Arginine Acetate
D017434	Protein Structure, Tertiary	The level of protein structure in which combinations of secondary protein structures (ALPHA HELICES; BETA SHEETS; loop regions, and AMINO ACID MOTIFS) pack together to form folded shapes. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure.	Tertiary Protein Structure,Protein Structures, Tertiary,Tertiary Protein Structures
D051046	Amino-Acid N-Acetyltransferase	A mitochondrial matrix enzyme that catalyzes the synthesis of L-GLUTAMATE to N-acetyl-L-glutamate in the presence of ACETYL-COA.	Acetyl CoA Glutamate N-Acetyltransferase,Acetyl Coenzyme A Glutamate N-Acetyltransferase,Amino Acid Acetyltransferase,Amino-Acid Acetyltransferase,N-Acetyl-L-Glutamate Synthetase,N-Acetylglutamate Synthase,N-Acetylglutamate Synthetase,Acetyl CoA Glutamate N Acetyltransferase,Acetyl Coenzyme A Glutamate N Acetyltransferase,Acetyltransferase, Amino Acid,Acetyltransferase, Amino-Acid,Acid Acetyltransferase, Amino,Amino Acid N Acetyltransferase,N Acetyl L Glutamate Synthetase,N Acetylglutamate Synthase,N Acetylglutamate Synthetase,N-Acetyltransferase, Amino-Acid,Synthase, N-Acetylglutamate,Synthetase, N-Acetyl-L-Glutamate,Synthetase, N-Acetylglutamate
D025461	Feedback, Physiological	A mechanism of communication with a physiological system for homeostasis, adaptation, etc. Physiological feedback is mediated through extensive feedback mechanisms that use physiological cues as feedback loop signals to control other systems.	Feedback, Biochemical,Feedback Inhibition, Biochemical,Feedback Regulation, Biochemical,Feedback Stimulation, Biochemical,Negative Feedback, Biochemical,Positive Feedback, Biochemical,Biochemical Feedback,Biochemical Feedback Inhibition,Biochemical Feedback Inhibitions,Biochemical Feedback Regulation,Biochemical Feedback Regulations,Biochemical Feedback Stimulation,Biochemical Feedback Stimulations,Biochemical Feedbacks,Biochemical Negative Feedback,Biochemical Negative Feedbacks,Biochemical Positive Feedback,Biochemical Positive Feedbacks,Feedback Inhibitions, Biochemical,Feedback Regulations, Biochemical,Feedback Stimulations, Biochemical,Feedback, Biochemical Negative,Feedback, Biochemical Positive,Feedbacks, Biochemical,Feedbacks, Biochemical Negative,Feedbacks, Biochemical Positive,Feedbacks, Physiological,Inhibition, Biochemical Feedback,Inhibitions, Biochemical Feedback,Negative Feedbacks, Biochemical,Physiological Feedback,Physiological Feedbacks,Positive Feedbacks, Biochemical,Regulation, Biochemical Feedback,Regulations, Biochemical Feedback,Stimulation, Biochemical Feedback,Stimulations, Biochemical Feedback