Amino Acids p. 1567 - 1576 (2012)
Update date:2022-08-10
Topics:
Ito, Tomokazu
Murase, Hirotaka
Maekawa, Motoki
Goto, Masaru
Hayashi, Shuhei
Saito, Hajime
Maki, Masatoshi
Hemmi, Hisashi
Yoshimura, Tohru
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 Apyridoxal 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 Arole 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 Mg2+ and Ca2+, which are well-known activators for the mammalian serine racemase. Mg2+ or Na+ binding caused two- to ninefold enhancement of the rates of both racemization and dehydration. The half-maximal activation concentrations of Mg2+ and Na+ were determined to be 1.2 μM and 2.2 mM, respectively. In the l-serine dehydrase reaction, Mg2+ and Na + enhanced the k cat value without changing the K m value. Alanine mutation of the residues E207 and D213, which correspond to the Mg2+-binding site of Schizosaccharomyces pombe serine racemase, abolished the Mg2+- and Na+-dependent stimulation. These results suggest that Mg2+ and Na+ share the common metal ion-binding site.
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