PMID:12005432

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Citation

Ramón-Maiques, S, Marina, A, Gil-Ortiz, F, Fita, I and Rubio, V (2002) Structure of acetylglutamate kinase, a key enzyme for arginine biosynthesis and a prototype for the amino acid kinase enzyme family, during catalysis. Structure 10:329-42

Abstract

N-Acetyl-L-glutamate kinase (NAGK), a member of the amino acid kinase family, catalyzes the second and frequently controlling step of arginine synthesis. The Escherichia coli NAGK crystal structure to 1.5 A resolution reveals a 258-residue subunit homodimer nucleated by a central 16-stranded molecular open beta sheet sandwiched between alpha helices. In each subunit, AMPPNP, as an alphabetagamma-phosphate-Mg2+ complex, binds along the sheet C edge, and N-acetyl-L-glutamate binds near the dyadic axis with its gamma-COO- aligned at short distance from the gamma-phosphoryl, indicating associative phosphoryl transfer assisted by: (1) Mg2+ complexation; (2) the positive charges on Lys8, Lys217, and on two helix dipoles; and (3) by hydrogen bonding with the y-phosphate. The structural resemblance with carbamate kinase and the alignment of the sequences suggest that NAGK is a structural and functional prototype for the amino acid kinase family, which differs from other acylphosphate-making devices represented by phosphoglycerate kinase, acetate kinase, and biotin carboxylase.

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Keywords

Amino Acid Sequence; Arginine/biosynthesis; Binding Sites; Catalysis; Crystallography, X-Ray; Dimerization; Escherichia coli/enzymology; Molecular Sequence Data; Molecular Structure; Multigene Family; Phosphotransferases (Carboxyl Group Acceptor)/chemistry; Phosphotransferases (Carboxyl Group Acceptor)/genetics; Phosphotransferases (Carboxyl Group Acceptor)/metabolism; Protein Structure, Secondary; Protein Structure, Tertiary; Sequence Alignment

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