Identification of imidazole as l‐arginine‐competitive inhibitor of porcine brain nitric oxide synthase

FEBS Letters

Werner, Ernst R.¹  Klatt, Peter²  Schmidt, Kurt²  Mayer, Bernd² 

[1] Institut für Medizinische Chemie und Biochemie, Universität Innsbruck, Fritz-Pregl-Straé 3, A-6020 Innsbruck, Austria;Institut für Pharmakologie und Toxikologie, Karl-Franzens-Universität Graz, Universitätsplatz 2, A-8010 Graz, Austria

关键词: Nitric oxide synthase;    Cytochrome P450;    Hydrogen peroxide;    Imidazole;    Radioligand binding;    Enzyme kinetics;    NOS;    nitric oxide synthase;    l-NNA;    N G-nitro-l-arginine;    H4biopterin;    (6R)-5;    6;    7;    8-tetrahydro-l-biopterin;    IC50;    concentration producing half-maximal inhibition;   

DOI  :  10.1016/0014-5793(94)00766-7

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Imidazole acts as a heme-site inhibitor of nitric oxide synthase (NOS). We used this compound to investigate whether the substrate l-arginine binds directly to the heme or to a separate domain of brain NOS. Enzyme kinetic experiments showed that imidazole enhanced the apparent K _m for l-arginine without affecting maximal enzyme activity, and binding studies revealed that the inhibitor displaced the radioligand N ^G-nitro-l-[³H]arginine in a concentration-dependent fashion. These results demonstrate that imidazole exerts its effects on NOS in an l-arginine-competitive manner and that the substrate site of the enzyme may be identical with the prosthetic heme group.

【 授权许可】

Unknown