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- Title
Metal ion dependency of serine racemase from Dictyostelium discoideum.
- Authors
Ito, Tomokazu; Murase, Hirotaka; Maekawa, Motoki; Goto, Masaru; Hayashi, Shuhei; Saito, Hajime; Maki, Masatoshi; Hemmi, Hisashi; Yoshimura, Tohru
- Abstract
d-Serine is known to act as an endogenous co-agonist of the N-methyl- d-aspartate receptor in the mammalian brain and is endogenously synthesized from l-serine by a pyridoxal 5′-phosphate-dependent enzyme, serine racemase. Though the soil-living mycetozoa Dictyostelium discoideum possesses no genes homologous to that of NMDA receptor, it contains genes encoding putative proteins relating to the d-serine metabolism, such as serine racemase, d-amino acid oxidase, and d-serine dehydratase. D. discoideum is an attractive target for the elucidation of the unknown functions of d-serine such as a role in cell development. As part of the elucidation of the role of d-serine in D. discoideum, we cloned, overexpressed, and examined the properties of the putative serine racemase exhibiting 46% amino acid sequence similarity with the human enzyme. The enzyme is unique in its stimulation by monovalent cations such as Na in addition to Mg and Ca, which are well-known activators for the mammalian serine racemase. Mg or Na binding caused two- to ninefold enhancement of the rates of both racemization and dehydration. The half-maximal activation concentrations of Mg and Na were determined to be 1.2 μM and 2.2 mM, respectively. In the l-serine dehydrase reaction, Mg and Na enhanced the k value without changing the K value. Alanine mutation of the residues E207 and D213, which correspond to the Mg-binding site of Schizosaccharomyces pombe serine racemase, abolished the Mg- and Na-dependent stimulation. These results suggest that Mg and Na share the common metal ion-binding site.
- Subjects
DICTYOSTELIUM discoideum; METAL ions; RACEMASES; BRAIN physiology; ASPARTATE receptors; METHYL aspartate receptors; ENZYME metabolism
- Publication
Amino Acids, 2012, Vol 43, Issue 4, p1567
- ISSN
0939-4451
- Publication type
Article
- DOI
10.1007/s00726-012-1232-z