Regulation of the monomer-dimer equilibrium in inducible nitric-oxide synthase by nitric oxide

David Li, Eric Y. Hayden, Koustubh Panda, Dennis J. Stuehr, Haiteng Deng, Denis L. Rousseau, Syun Ru Yeh

Research output: Contribution to journalArticlepeer-review

29 Scopus citations


The oxygenase domain of inducible nitric-oxide synthase exists as a functional tight homodimer in the presence of the substrate L-arginine and the cofactor tetrahydrobiopterin (H4B). In the absence of H4B, the enzyme is a mixture of monomer and loose dimer. We show that exposure of H4B-free enzyme to NO induces dissociation of the loose dimer into monomers in a reaction that follows single exponential decay kinetics with a lifetime of ∼300 min. It is followed by a faster autoreduction reaction of the heme iron with a lifetime of ∼30 min and the concurrent breakage of the proximal iron-thiolate bond, forming a five-coordinate NO-bound ferrous species. Mass spectrometry revealed that the NO-induced monomerization is associated with intramolecular disulfide bond formation between Cys104 and Cys109, located in the zinc-binding motif. The regulatory effect of NO as a dimer inhibitor is discussed in the context of the structure/function relationships of this enzyme.

Original languageEnglish (US)
Pages (from-to)8197-8204
Number of pages8
JournalJournal of Biological Chemistry
Issue number12
StatePublished - Mar 24 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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