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

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

Research output: Contribution to journalArticlepeer-review

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 5-nitrosylation. NMDA receptor physiologically enhances SR S-nitrosylation by activating neuronal nitricoxide 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.

Original languageEnglish (US)
Pages (from-to)2950-2955
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number8
DOIs
StatePublished - Feb 20 2007

Keywords

  • NMDA receptor
  • Neuronal nitric-oxide synthase
  • S-nitrosylation

ASJC Scopus subject areas

  • General

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