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

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.

SUBMITTER: Mustafa AK

PROVIDER: S-EPMC1815287 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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

Mustafa Asif K AK Kumar Manish M Selvakumar Balakrishnan B Ho Gary P H GP Ehmsen Jeffrey T JT Barrow Roxanne K RK Amzel L Mario LM Snyder Solomon H SH

Proceedings of the National Academy of Sciences of the United States of America 20070209 8

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 ...[more]

PMID: 17293453

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