Differences between two active forms of CO-bound soluble guanylate cyclase in the presence of activators and substrate and their populations revealed by resonance Raman spectroscopy

Abstract

Soluble guanylate cyclase is a dimeric (ab) enzyme catalyzing the conversion of GTP to cyclic GMP which acts as a second messenger in cellular signaling. It is the only known physiological receptor of NO and binding of NO to its heme, which is covalently bound via a conserved His-b105, activates this enzyme several hundred folds over its basal level. It is known that NO-binding causes the cleavage of Fe-His bond. CO marginally activates sGC, and in the presence of some activator molecules like YC-1 and BAY it activates to the same level as NO-bound sGC, although a mechanism of this synergistic effect is hardly understood. Herein, we present evidences for the presence of two forms of CO-bound sGC in the presence of activators and deduce their structural differences and population on the basis of resonance Raman spectroscopy. A mechanism for the synergetic effect has been discussed.