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Nitric oxide S -nitrosylates serine racemase, mediating feedback inhibition of d -serine formation

2007; National Academy of Sciences; Volume: 104; Issue: 8 Linguagem: Inglês

10.1073/pnas.0611620104

1091-6490

Asif K. Mustafa, Manish Kumar, B Selvakumar, Gary P. H. Ho, Jeffrey T. Ehmsen, Roxanne K. Barrow, L. Mario Amzel, Solomon H. Snyder,

Neuroscience and Neuropharmacology Research

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.