Cellular Factors That Shape the Activity or Function of Nitric Oxide-Stimulated Soluble Guanylyl Cyclase

Figures

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  Figure 1. Structural changes of SGC in response to NO-dependent activation. (A): Schematic representation of the process of NO:-SGC adduct formation. The five-coordinate heme moiety of SGC (state a) binds NO to form a six-coordinate complex (state b). The six-coordinate complex subsequently converts irreversibly into a five-coordinate complex (state c) due to the rupture of Fe-His105 bond. Corresponding reaction rates are indicated. (B): Structural rearrangement of different SGC domains that occurs following NO binding causes significant activation of cGMP-forming activity.

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  Figure 2. Alternative hypothesis of the allosteric effect of additional NO. In the presence of NO excess, the five-coordinate NO-heme adduct (state A) may bind a second NO to form a transient ternary complex (state B), which rapidly loses the distal NO and converts into a five-coordinate NO-heme adduct with NO bound on the proximal side of heme (state C). Alternatively, the allosteric effect of additional NO is explained by S-nitrosylation of an unspecified cysteine residue (state D), resulting in a full stimulation cGMP-forming activity.