Butyl isocyanide as a probe of the activation mechanism of soluble guanylate cyclase. Investigating the role of non-heme nitric oxide

J Biol Chem. 2007 Dec 7;282(49):35741-8. doi: 10.1074/jbc.M705557200. Epub 2007 Oct 4.


Nitric oxide (NO) is a physiologically relevant activator of the hemoprotein soluble guanylate cyclase (sGC). In the presence of NO, sGC is activated several hundredfold above the basal level by a mechanism that remains to be elucidated. The heme ligand n-butyl isocyanide (BIC) was used to probe the mechanism of NO activation of sGC. Electronic absorption spectroscopy was used to show that BIC binds to the sGC heme, forming a 6-coordinate complex with an absorbance maximum at 429 nm. BIC activates sGC 2-5-fold, and synergizes with the allosteric activator YC-1, to activate the enzyme 15-25-fold. YC-1 activates the sGC-BIC complex, and leads to an increase in both the V(max) and K(m). BIC was also used to probe the mechanism of NO activation. The activity of the sGC-BIC complex increases 15-fold in the presence of NO, without displacing BIC at the heme, which is consistent with previous reports that proposed the involvement of a non-heme NO binding site in the activation process.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Binding Sites
  • Enzyme Activation
  • Guanylate Cyclase / chemistry*
  • Heme / chemistry*
  • Isocyanates / chemistry*
  • Ligands
  • Nitric Oxide / chemistry*
  • Spectroscopy, Electron Energy-Loss


  • Isocyanates
  • Ligands
  • Nitric Oxide
  • Heme
  • Guanylate Cyclase
  • butyl isocyanate