Fig. 1: Domain architecture and organization of human PKG1.

a PKG1α constructed monomer highlighting domains and subdomains as correspond to the schematic representation (b) of the domains with α visualized on top and β underneath. The domain residue boundaries for each isoform are indicated. The regulatory domain consists of a dimerization subdomain and cGMP-Binding subdomain. The dimerization subdomain consists of a Leucine Zipper (LZ) and auto-inhibitory region (AI) which plays a role in protein regulation via the Pseudo-Substrate (PS). While the cGMP-binding subdomain consists of a high (CNB-A) and low-affinity (CNB-B) cyclic nucleotide binding sites which directly bind cGMP. Progressive binding of cGMP to these sites ultimately causes release of the AI domain, and extension of the catalytic domain away from the regulatory domain allowing for ATP-mediated substrate catalysis. c The aligned sequences of α and β dimerization domains is visible. All differences in sequence between the two variants are restricted to this subdomain. A sequence similarity histogram is overlayed with high similarity indicated as bars above the line and low or no similarity as bars below the line.