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

FEBS Letters

Schmidt, Kurt¹  Hemmens, Benjamin¹  Völker, Christof¹  Woschitz, Silvia¹  Mayer, Bernd¹  Klösch, Burkhardt¹  Pitters, Eva¹ 

[1] Institut für Pharmakologie und Toxikologie, Karl-Franzens Universität Graz, Universitätsplatz 2, A-8010 Graz, Austria

关键词: Nitric oxide;    Nitric oxide synthase;    Dimerization;    Isoenzyme;    Inhibitor protein;    NOS;    nitric oxide synthase;    nNOS;    neuronal nitric oxide synthase (type I);    iNOS;    inducible nitric oxide synthase (type II);    eNOS;    endothelial nitric-oxide synthase (type III);    H4biopterin;    (6R)-5;    6;    7;    8-tetrahydro-l-biopterin=(6R)-5;    6;    7;    8-tetrahydro-6-(l-erythro-1;    2-dihydroxypropyl)pteridine;    PIN;    protein inhibitor of nNOS;    GST-PIN;    fusion protein of PIN with glutathione S-transferase;   

DOI  :  10.1016/S0014-5793(98)00704-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM GST-PIN with 63 nM nNOS after 30 min at 37°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.

【 授权许可】

Unknown