ELECTRON-PARAMAGNETIC-RESONANCE SPECTROSCOPY OF THE HEME DOMAIN OF INDUCIBLE NITRIC-OXIDE SYNTHASE - BINDING OF LIGANDS AT THE ARGININE SITE INDUCES CHANGES IN THE HEME LIGATION GEOMETRY

The electron paramagnetic resonance spectra of the heme domain of indu cible nitric oxide synthase (iNOS) demonstrate a close relationship to the corresponding spectra of the neuronal isoform (nNOS). The binding of ligands to the iNOS arginine site perturbs the environment of the high-spin ferriheme in a highly ligand-specific manner. The iNOS forms five-coordinate, high-spin complexes with arginine analogs which are clearly related to the corresponding complexes of nNOS. Studies indica te that the binding of L-arginine, N-omega-hydroxy-L-arginine (NHA), a nd N-omega-methyl-L-arginine (NMA) produces various spectroscopic spec ies closely corresponding to the equivalent complexes of nNOS, while N -omega-nitro-L-arginine (NNA) binding produces a state which appears i ntermediate in character between the nNOS NNA and arginine complexes. These spectroscopic studies have permitted the determination of ligand -specific high-spin states which reveal similarities and differences b etween iNOS and nNOS.