Mutation in the flavin mononucleotide domain modulates magnetic circular dichroism spectra of the iNOS ferric cyano complex in a substrate-specific manner

Joseph Sempombe, Mary Grace I. Galinato, Bradley O. Elmore, Weihong Fan, J. Guy Guillemette, Nicolai Lehnert, Martin L. Kirk, Changjian Feng

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11 Scopus citations

Abstract

We have obtained low-temperature magnetic circular dichroism (MCD) spectra for ferric cyano complexes of the wild type and E546N mutant of a human inducible nitric oxide synthase (iNOS) oxygenase/flavin mononucleotide (oxyFMN) construct. The mutation at the FMN domain has previously been shown to modulate the MCD spectra of the l-arginine-bound ferric iNOS heme (Sempombe, J.; et al. J. Am. Chem. Soc.2009, 131, 6940-6941). The addition of l-arginine to the wild-type protein causes notable changes in the CN --adduct MCD spectrum, while the E546N mutant spectrum is not perturbed. Moreover, the MCD spectral perturbation observed with l-arginine is absent in the CN - complexes incubated with N-hydroxy-l-arginine, which is the substrate for the second step of NOS catalysis. These results indicate that interdomain FMN-heme interactions exert a long-range effect on key heme axial ligand-substrate interactions that determine substrate oxidation pathways of NOS.

Original languageEnglish (US)
Pages (from-to)6859-6861
Number of pages3
JournalInorganic chemistry
Volume50
Issue number15
DOIs
StatePublished - Aug 1 2011

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Inorganic Chemistry

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