title: A novel pyridoxal 5'-phosphate-dependent amino acid racemase in the Aplysia californica central nervous system.
abstract: D-aspartate (D-Asp) is found in specific neurons, transported to neuronal terminals and released in a stimulation-dependent manner. Because D-Asp formation is not well understood, determining its function has proved challenging. Significant levels of D-Asp are present in the cerebral ganglion of the F- and C-clusters of the invertebrate Aplysia californica, and D-Asp appears to be involved in cell-cell communication in this system. Here, we describe a novel protein, DAR1, from A. californica that can convert aspartate and serine to their other chiral form in a pyridoxal 5'-phosphate (PLP)-dependent manner. DAR1 has a predicted length of 325 amino acids and is 55% identical to the bivalve aspartate racemase, EC 5.1.1.13, and 41% identical to the mammalian serine racemase, EC 5.1.1.18. However, it is only 14% identical to the recently reported mammalian aspartate racemase, DR, which is closely related to glutamate-oxaloacetate transaminase, EC 2.6.1.1. Using whole-mount immunohistochemistry staining of the A. californica central nervous system, we localized DAR1-like immunoreactivity to the medial region of the cerebral ganglion where the F- and C-clusters are situated. The biochemical and functional similarities between DAR1 and other animal serine and aspartate racemases make it valuable for examining PLP-dependent racemases, promising to increase our knowledge of enzyme regulation and ultimately, D-serine and D-Asp signaling pathways.
authors.affiliation: Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.forename: Nobutoshi
authors.initials: N
authors.lastname: Ota
authors.forename: Elena V
authors.initials: EV
authors.lastname: Romanova
authors.forename: Jonathan V
authors.initials: JV
authors.lastname: Sweedler
mesh_terms: D000591:Amino Acid Isomerases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001048:Aplysia / Q000201:enzymology*; D001224:Aspartic Acid / Q000235:genetics / Q000378:metabolism*; D009420:Nervous System / Q000201:enzymology*; D011732:Pyridoxal Phosphate / Q000235:genetics / Q000378:metabolism*; D012694:Serine / Q000235:genetics / Q000378:metabolism*
chemical_list: D001224:Aspartic Acid; D012694:Serine; D011732:Pyridoxal Phosphate; D000591:Amino Acid Isomerases