The natural product noformycin is an inhibitor of inducible-nitric oxide synthase.
Inducible-Nitric oxide synthase (iNOS, EC 1.14.13.39) catalyzes the formation of nitric oxide (NO) and L-citrulline from L-Arg. NADPH and dioxygen. The natural product, (-)-noformycin was found to be a potent, competitive inhibitor of recombinant human iNOS with respect to L-Arg with a Ki = 1.3 +/- 0.3 microM. The reversible binding of noformycin caused a high spin type I spectral perturbation of the iNOS heme group with a Kd = 1.5 +/- 0.2 microM. These results demonstrate that natural products may be a useful source for inhibitors of NO-biosynthesis.
Green
B G
BG
Department of Enzymology, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Chabin
R
R
Grant
S K
SK
D001120:Arginine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011485:Protein Binding; D011759:Pyrrolidines / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013237:Stereoisomerism
D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D011994:Recombinant Proteins; C005642:noformicin; D001120:Arginine; D019001:Nitric Oxide Synthase