Molecular steps in soluble guanylate cyclase activation
© BioMed Central Ltd 2005
Published: 16 June 2005
Soluble guanylate cyclase (sGC) is a hemoprotein that is selectively activated by specifically binding NO. Once activated sGC synthesizes cyclic GMP from GTP which then triggers reactions essential to animal physiology. sGC essentially functions as a selective sensor for NO. sGC belongs to a recently identified group of proteins termed the H-NOX family (Heme Nitric oxide/OXygen binding proteins) that includes bacterial counterparts from aerobic and anaerobic organisms [1–4]. Based on our recent structure of a family member , a molecular basis for the ligand discrimination against O2 in NO-regulated sGCs has been established. Further studies have pointed towards O2-regulated sGCs in C. elegans . NO binding to the heme remains as a key molecular activation step; however, it has become clear that activation and deactivation are regulated in a complex manner [6, 7]. In the accepted model shown below, NO binds to the sGC heme, activating the enzyme after conversion to the 5-coordinate nitrosyl complex.
We gratefully acknowledge financial support from the Aldo DeBenedictis Fund, LDRD fund from the Lawrence Berkeley National Laboratory and the National Institutes of Health.
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