PDE3

phosphodiesterase 3A, cGMP-inhibited
Identifiers
Symbol	PDE3A
Entrez	5139
HUGO	8778
OMIM	123805
RefSeq	NM_000921
UniProt	Q14432
Other data
Locus	Chr. 12 p12

phosphodiesterase 3B, cGMP-inhibited
Identifiers
Symbol	PDE3B
Entrez	5140
HUGO	8779
OMIM	602047
RefSeq	NM_000922
UniProt	Q13370
Other data
Locus	Chr. 11 p15.2

PDE3 is a phosphodiesterase. The PDEs belong to at least eleven related gene families, which are different in their primary structure, substrate affinity, responses to effectors, and regulation mechanism. Most of the PDE families are composed of more than one gene. PDE3 is clinically significant because of its role in regulating heart muscle, vascular smooth muscle and platelet aggregation. PDE3 inhibitors have been developed as pharmaceuticals, but their use is limited by arrhythmic effects and they can increase mortality in some applications.

The mammalian PDEs share a common structural organization and contain three functional domains, which include the conserved catalytic core, a regulatory N-terminus, and the C-terminus. The conserved catalytic core is much more similar within PDE families, with about 80% amino acid identity, than between different families. It is believed that the core contains common structural elements that are important for the hydrolysis of cAMP and cGMP phosphodiester bonds. It is also believed that it contains family-specific determinants for differences in affinity for substrates and sensitivity for inhibitors.
The catalytic domain of PDE3 is characterized by a 44-amino acid insert, but this insert is unique to the PDE3 family, and is a factor when determining a structure for a potent and selective PDE3 inhibitor.
The crystal structure of the catalytic domains of several PDEs, including PDE3B, have shown that they contain three helical subdomains :

At the interface of these domains a deep hydrophobic pocket is formed by residues that are highly conserved among all PDEs. This pocket is the active site and is composed of four subsites :

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Wikipedia