The catalytic domains of PDE1 (and other types of PDEs) have three helical subdomains: an N-terminal cyclin-fold region, a linker region and a C-terminal helical bundle. A deep hydrophobic pocket is formed at the interface of these subdomains. It is composed of four subsites. They are: a metal binding site (M site), core pocket (Q pocket), hydrophobic pocket (H pocket) and lid region (L region). The M site is placed at the bottom of the hydrophobic pocket with several metal atoms. The metal atoms bind to residues that are completely conserved in all PDE family members. The identity of the metal atoms is not known with absolute certainty. However, some evidence indicate that at least one of the metals is zinc and the other is likely to be magnesium. The zinc coordination sphere is composed of three histidines, one aspartate and two water molecules. The magnesium coordination sphere involves the same aspartate along with five water molecules, one of which is shared with the zinc molecule. The reputed role of the metal ions include structure stabilization as well as activation of hydroxide to mediate catalysis.