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

Proc Natl Acad Sci U S A. 2007 Feb 20;104(8):2950-5. doi: 10.1073/pnas.0611620104. Epub 2007 Feb 9.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Amino Acid Sequence
  • Animals
  • Coenzymes / metabolism
  • Cysteine / metabolism
  • Enzyme Activation / drug effects
  • Feedback, Physiological / drug effects*
  • Humans
  • Mice
  • Models, Molecular
  • Models, Neurological
  • Molecular Sequence Data
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Synthase Type I / metabolism
  • Racemases and Epimerases / chemistry
  • Racemases and Epimerases / metabolism*
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • S-Nitrosoglutathione / pharmacology*
  • Serine / biosynthesis*


  • Coenzymes
  • Receptors, N-Methyl-D-Aspartate
  • Nitric Oxide
  • Serine
  • S-Nitrosoglutathione
  • Adenosine Triphosphate
  • Nitric Oxide Synthase Type I
  • Racemases and Epimerases
  • serine racemase
  • Cysteine