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

doi:10.1073/pnas.0611620104

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

113 Scopus citations

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 language	English (US)
Pages (from-to)	2950-2955
Number of pages	6
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	104
Issue number	8
DOIs	https://doi.org/10.1073/pnas.0611620104
State	Published - Feb 20 2007

Keywords

NMDA receptor
Neuronal nitric-oxide synthase
S-nitrosylation

ASJC Scopus subject areas

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10.1073/pnas.0611620104

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title = "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 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.",

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AU - Mustafa, Asif K.

AU - Kumar, Manish

AU - Selvakumar, Balakrishnan

AU - Ho, Gary P.H.

AU - Ehmsen, Jeffrey T.

AU - Barrow, Roxanne K.

AU - Amzel, L. Mario

AU - Snyder, Solomon H.

PY - 2007/2/20

Y1 - 2007/2/20

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AB - 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.

KW - NMDA receptor

KW - Neuronal nitric-oxide synthase

KW - S-nitrosylation

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

Abstract

Keywords

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