Molecular aspects of the three isoforms of nitric oxide synthase that uniquely suit them for no. production

I. B.S.S. Masters, P. Martasek, L. J. Roman, J. S. Nishimura, R. T. Miller, J. C. Salerno, S. S. Gross

Research output: Contribution to journalArticle

Abstract

The three genetically encoded isoforms of nitric oxide synthase (NOS) in mammals are differentially expressed in various cells and tissues. Neuronal (nNOS) and endothelial (eNOS) isoforms are constitutively expressed and the inducible (iNOS) isoform is induced by various cytokines: Structural differences among these isoforms are being studied by a variety of biophysical techniques [electron paramagnetic spectroscopy (EPR), absorbance, fluorescence, and circular dichroism (CD) spectroscopy, and X-ray crystallography]. We have used optical difference spectroscopy to determine binding constants for substrate analogs and inhibitors of all three isoforms, and EPR to define the environment of the heine iron in each case. Spectral perturbations of each NOS isoform indicate that the heme environments are unique. N%methyI-L-arginine (NMA), a relatively poor inhibitor of eNOS, produces an EPR signal with eNOS indicating lower rhombicity than NMA complexes of either nNOS or iNOS. N%nitro-L-arginine (NNA) binds to iNOS less tightly than to eNOS or nNOS, not forming the lower rhombicity NNA complex characteristic of nNOS. Various modular constructs and mutants of the three isoforms have led to identification of modules of the isoforms involved in cofactor binding.

Original languageEnglish (US)
Pages (from-to)A1009
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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