A molecular view of the regulation of sGC activity

Mammalian sGC is a heterodimer composed of α- and β-subunits (Figure 1). The C-terminus of each subunit contains a catalytic domain and the active site is composed of residues from both subunits. The catalytic domains also form a pseudosymmetric active site that contains residues known to be involved in nucleotide binding, but lack the amino acids required for catalysis. Sequence analysis shows that each subunit also contains well-defined PAS-like domain, and a predicted helical region. The N-termini of the α- and β-subunits are homologous to the H-NOX (H eme-N itric oxide/OX ygen) family of proteins. The N-terminus of β-subunit contains a ferrous heme cofactor that serves a receptor for NO. sGC activity is also modulated by ATP and the substrate GTP and recent studies point toward a more complicated role for NO in the regulation of activity. Structural results coupled with biochemical and cellular experiments have broadened the current molecular view of the regulation of sGC.

Figure 1

Domain structure of sGC.