title: N-acetylaspartylglutamate synthetase II synthesizes N-acetylaspartylglutamylglutamate.
abstract: N-Acetylaspartylglutamate (NAAG) is found at high concentrations in the vertebrate nervous system. NAAG is an agonist at group II metabotropic glutamate receptors. In addition to its role as a neuropeptide, a number of functions have been proposed for NAAG, including a role as a non-excitotoxic transport form of glutamate and a molecular water pump. We recently identified a NAAG synthetase (now renamed NAAG synthetase I, NAAGS-I), encoded by the ribosomal modification protein rimK-like family member B (Rimklb) gene, as a member of the ATP-grasp protein family. We show here that a structurally related protein, encoded by the ribosomal modification protein rimK-like family member A (Rimkla) gene, is another NAAG synthetase (NAAGS-II), which in addition, synthesizes the N-acetylated tripeptide N-acetylaspartylglutamylglutamate (NAAG(2)). In contrast, NAAG(2) synthetase activity was undetectable in cells expressing NAAGS-I. Furthermore, we demonstrate by mass spectrometry the presence of NAAG(2) in murine brain tissue and sciatic nerves. The highest concentrations of both, NAAG(2) and NAAG, were found in sciatic nerves, spinal cord, and the brain stem, in accordance with the expression level of NAAGS-II. To our knowledge the presence of NAAG(2) in the vertebrate nervous system has not been described before. The physiological role of NAAG(2), e.g. whether it acts as a neurotransmitter, remains to be determined.
authors: Institute of Biochemistry and Molecular Biology, University of Bonn, D-53115 Bonn, Germany.
authors: Julia
authors: J
authors: Lodder-Gadaczek
authors: Ivonne
authors: I
authors: Becker
authors: Volkmar
authors: V
authors: Gieselmann
authors: Lihua
authors: L
authors: Wang-Eckhardt
authors: Matthias
authors: M
authors: Eckhardt
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D043402:Cathepsin A / Q000737:chemistry; D006224:Cricetinae; D003412:Cricetulus; D004151:Dipeptides / Q000096:biosynthesis; D043425:Glutamate Carboxypeptidase II / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids / Q000378:metabolism; D012584:Sciatic Nerve / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods
chemical_list: D004151:Dipeptides; C027172:isospaglumic acid; D043402:Cathepsin A; D043425:Glutamate Carboxypeptidase II