The protein inhibitor of neuronal nitric oxide synthase (PIN): characterization of its action on pure nitric oxide synthases

FEBS Lett. 1998 Jul 3;430(3):397-400. doi: 10.1016/s0014-5793(98)00704-2.

Abstract

Neuronal NO synthase (nNOS) was discovered recently to interact specifically with the protein PIN (protein inhibitor of nNOS) [Jaffrey, S.R. and Snyder, S.H. (1996) Science 274, 774-777]. We have studied the effects on pure NOS enzymes of the same GST-tagged PIN used in the original paper. Unexpectedly, all NOS isoenzymes were inhibited. The IC50 for nNOS was 18 +/- 6 microM GST-PIN with 63 nM nNOS after 30 min at 37 degrees C. Uncoupled NADPH oxidation was inhibited similarly, whereas cytochrome c reductase activity, the K(M) for L-arginine, and dimerization were unaffected. We reconsider the physiological role of PIN in the light of these results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / pharmacology*
  • Cytochrome c Group / metabolism
  • Dimerization
  • Drosophila Proteins*
  • Dyneins
  • Enzyme Inhibitors / pharmacology
  • NADP / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors*
  • Nitric Oxide Synthase / chemistry
  • Nitric Oxide Synthase / metabolism
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Oxidation-Reduction
  • Rats
  • Recombinant Fusion Proteins

Substances

  • Carrier Proteins
  • Cytochrome c Group
  • Drosophila Proteins
  • Enzyme Inhibitors
  • Recombinant Fusion Proteins
  • NADP
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos1 protein, rat
  • Nos2 protein, rat
  • Nos3 protein, rat
  • Dyneins