一氧化氮对丝氨酸消旋酶进行S-亚硝基化，介导对D-丝氨酸形成的反馈抑制。
Nitric oxide S-nitrosylates serine racemase, mediating feedback inhibition of D-serine formation.
作者信息
Mustafa Asif K, Kumar Manish, Selvakumar Balakrishnan, Ho Gary P H, Ehmsen Jeffrey T, Barrow Roxanne K, Amzel L Mario, Snyder Solomon H
机构信息
Solomon H. Snyder Department of Neuroscience, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2950-5. doi: 10.1073/pnas.0611620104. Epub 2007 Feb 9.
Abstract
Serine racemase (SR) generates D-serine, a coagonist with glutamate 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.
摘要
丝氨酸消旋酶（SR）可生成D-丝氨酸，它是N-甲基-D-天冬氨酸（NMDA）受体处与谷氨酸协同作用的激动剂。我们发现，SR在生理条件下会发生S-亚硝基化，从而导致酶活性受到显著抑制。这种抑制作用涉及与辅因子ATP的相互作用，这反映出ATP结合位点与生理S-亚硝基化位点半胱氨酸-113（C113）相邻。NMDA受体通过激活神经元型一氧化氮合酶（nNOS）在生理条件下增强SR的S-亚硝基化。这些发现支持了一种模型，即突触后一氧化氮（NO）生成的刺激反馈至突触前细胞，使SR发生S-亚硝基化，并减少突触后NMDA受体可利用的D-丝氨酸。
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Neuron-derived D-serine release provides a novel means to activate N-methyl-D-aspartate receptors.神经元衍生的D-丝氨酸释放提供了一种激活N-甲基-D-天冬氨酸受体的新方法。
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Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity.丝氨酸消旋酶通过α,β-消除活性调节细胞内D-丝氨酸水平。
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Novel neural modulators.新型神经调节剂。
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