Nitric oxide S -nitrosylates serine racemase, mediating feedback inhibition of d -serine formation
- 20 February 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 104 (8) , 2950-2955
- https://doi.org/10.1073/pnas.0611620104
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.Keywords
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