PMID- 21343289 OWN - NLM STAT- MEDLINE DCOM- 20110628 LR - 20211020 IS - 1083-351X (Electronic) IS - 0021-9258 (Print) IS - 0021-9258 (Linking) VI - 286 IP - 15 DP - 2011 Apr 15 TI - A novel pyridoxal 5'-phosphate-dependent amino acid racemase in the Aplysia californica central nervous system. PG - 13765-74 LID - 10.1074/jbc.M110.178228 [doi] AB - 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. FAU - Wang, Liping AU - Wang L AD - Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA. FAU - Ota, Nobutoshi AU - Ota N FAU - Romanova, Elena V AU - Romanova EV FAU - Sweedler, Jonathan V AU - Sweedler JV LA - eng GR - R01 NS031609/NS/NINDS NIH HHS/United States GR - NS031609/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20110222 PL - United States TA - J Biol Chem JT - The Journal of biological chemistry JID - 2985121R RN - 30KYC7MIAI (Aspartic Acid) RN - 452VLY9402 (Serine) RN - 5V5IOJ8338 (Pyridoxal Phosphate) RN - EC 5.1.1.- (Amino Acid Isomerases) SB - IM MH - Amino Acid Isomerases/genetics/*metabolism MH - Animals MH - Aplysia/*enzymology MH - Aspartic Acid/genetics/*metabolism MH - Nervous System/*enzymology MH - Pyridoxal Phosphate/genetics/*metabolism MH - Serine/genetics/*metabolism PMC - PMC3075720 EDAT- 2011/02/24 06:00 MHDA- 2011/06/29 06:00 PMCR- 2012/04/15 CRDT- 2011/02/24 06:00 PHST- 2011/02/24 06:00 [entrez] PHST- 2011/02/24 06:00 [pubmed] PHST- 2011/06/29 06:00 [medline] PHST- 2012/04/15 00:00 [pmc-release] AID - S0021-9258(20)51755-9 [pii] AID - M110.178228 [pii] AID - 10.1074/jbc.M110.178228 [doi] PST - ppublish SO - J Biol Chem. 2011 Apr 15;286(15):13765-74. doi: 10.1074/jbc.M110.178228. Epub 2011 Feb 22.