For over 20 years it has been known that cGMP concentrations are increased by a wide variety of agents. The formation of cGMP from GTP is catalysed by guanylyl cyclase. Guanylyl cyclase is found in various cellular compartments of most organisms including animals, plants and bacteria, in soluble and/or membrane-bound forms (Drewett & Garbers, 1994). Membrane-bound guanylyl cyclase (mGC) is a single polypeptide which was first established by cloning and sequencing of the cDNA encoding a sea urchin sperm protein crosslinked to a sperm-activating peptide (SAP) IIA (Chinkers & Garbers, 1991). Soluble guanylyl cyclase (sGC) consists of two different subunits (alpha and beta). mGC is composed of an extracellular, a single transmembrane and an intracellular domain that is further divided into a protein-kinase-like domain and a cyclase catalytic domain. The primary structure of the catalytic domain of both mGC and sGC is highly conserved among vertebrates and invertebrates (Suzuki et al., 1999).
Inhibition of soluble guanylyl cyclase by small molecules targeting the catalytic domain
