Figure 2. Working model of PDE5.

The regulatory domain in the amino-terminal portion of PDE5 contains a phosphorylation site and two allosteric cGMP-binding sites, a and b, that are theorized to be involved in a cGMP negative-feedback loop. The catalytic domain in the carboxyl-terminal portion contains two Zn²⁺-binding motifs, A and B, and a cGMP-binding substrate site. cGMP, cyclic guanosine monophosphate; PDE5, phospho-diesterase type 5. Reproduced, with permission, from Ref. 6 © (1999) American Society for Biochemistry and Molecular Biology.