ＮＭＤＡ受容体に作用する神経伝達物質Ｄ体セリンを産出するセリンラセマーゼの結晶構造

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  • Crystal Structure of Serine Racemase that Produces Neurotransmitter D-Serine for Stimulation of the NMDA Receptor
  • NMDA ジュヨウタイ ニ サヨウ スル シンケイ デンタツ ブッシツ Dタイ セリン オ サンシュツ スル セリンラセマーゼ ノ ケッショウ コウゾウ

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d-Serine is an endogenous coagonist for the N-methyl-d-aspartate receptor and is involved in excitatory neurotransmission in the brain. Mammalian pyridoxal 5’-phosphate-dependent serine racemase, which is localized in the mammalian brain, catalyzes the racemization of l-serine to yield d-serine and vice versa. We have determined the structures of three forms of the mammalian enzyme homolog from Schizosaccharomyces pombe. Lys57 and Ser82 located on the protein and solvent sides, respectively, with respect to the cofactor plane, are acid-base catalysts that shuttle protons to the substrate. The modified enzyme, which has a unique lysino-d-alanyl residue at the active site, also binds the substrate serine in the active site, suggesting that the lysino-d-alanyl residue acts as a catalytic base in the same manner as Lys57 of the wild type enzyme.

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