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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition of D-serine formation
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Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition of D-serine formation

机译:一氧化氮S-亚硝酰基化丝氨酸消旋酶,介导D-丝氨酸形成的反馈抑制

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摘要

Serine racemase (SR) generates D-serine, a coagonist with gluta-mate at NMDA receptors. We show that SR is physiologically S-nitrosylated leading to marked inhibition of enzyme activity. Inhibition involves interactions with the cofactor ATP reflecting juxtaposition of the ATP-binding site and cysteine-113 (C113), the site for physiological S-nitrosylation. NMDA receptor physiologically enhances SR S-nitrosylation by activating neuronal nitric-oxide synthase (nNOS). These findings support a model whereby postsynaptic stimulation of nitric-oxide (NO) formation feeds back to presynaptic cells to S-nitrosylate SR and decrease D-serine availability to postsynaptic NMDA receptors.
机译:丝氨酸消旋酶(SR)产生D-丝氨酸,一种在NMDA受体上带有谷氨酸的激动剂。我们表明,SR是生理S-亚硝基化导致明显抑制酶活性。抑制作用涉及与辅助因子ATP的相互作用,反映了ATP结合位点与半胱氨酸113(C113)(生理学S-亚硝基化的位点)的并置。 NMDA受体通过激活神经元一氧化氮合酶(nNOS)在生理上增强SR S-亚硝基化。这些发现支持了一种模型,在该模型中,突触后一氧化氮(NO)形成的刺激反馈至突触前细胞,使S-亚硝酰SR反馈并降低D-丝氨酸对突触后NMDA受体的利用。

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