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

Mustafa, Asif K; Kumar, Manish; Selvakumar, Balakrishnan; Ho, Gary P H; Ehmsen, Jeffrey T; Barrow, Roxanne K; Amzel, L Mario; Snyder, Solomon H · Proc Natl Acad Sci U S A · 2007

basic_science · Level V

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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.

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