Publications [#232446] of Emily R. Derbyshire

Journal Articles

1. Derbyshire, ER; Marletta, MA, Butyl isocyanide as a probe of the activation mechanism of soluble guanylate cyclase. Investigating the role of non-heme nitric oxide., The Journal of biological chemistry, vol. 282 no. 49 (December, 2007), pp. 35741-35748, ISSN 0021-9258 [17916555], [doi]
   (last updated on 2024/12/31)

   Abstract:
   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.