THE NATURAL PRODUCT NOFORMYCIN IS AN INHIBITOR OF INDUCIBLE-NITRIC OXIDE SYNTHASE

Inducible-Nitric oxide synthase (iNOS, EC 1.14.13.39) catalyzes the fo rmation of nitric oxide (NO) and L-citrulline from L-Arg, NADPH and di oxygen. The natural product, (-)-noformycin was found to be a potent, competitive inhibitor of recombinant human iNOS with respect to L-Arg with a K-i = 1.3 +/- 0.3 mu M. The reversible binding of noformycin ca used a high spin type I spectral perturbation of the iNOS heme group w ith a K-d = 1.5 +/- 0.2 mu M. These results demonstrate that natural p roducts may be a useful source for inhibitors of NO-biosynthesis. (C) 1996 Academic Press, Inc.