Pathways & interactions
3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily (IPR036971)
Short name: PDEase_catalytic_dom_sf
- 3'5'-cyclic nucleotide phosphodiesterase, catalytic domain (IPR002073)
- HD/PDEase domain (IPR003607)
- 3'5'-cyclic nucleotide phosphodiesterase (IPR023088)
- 3'5'-cyclic nucleotide phosphodiesterase, conserved site (IPR023174)
The cyclic nucleotide phosphodiesterases (PDE) comprise a group of enzymes that degrade the phosphodiester bond in the second messenger molecules cAMP and cGMP. They are divided into 11 families. They regulate the localisation, duration and amplitude of cyclic nucleotide signalling within subcellular domains. PDEs are therefore important for signal transduction.
PDE enzymes are often targets for pharmacological inhibition due to their unique tissue distribution, structural properties, and functional properties. Inhibitors include: Roflumilast for chronic obstructive pulmonary disease and asthma [PMID: 18447606], Sildenafil for erectile dysfunction [PMID: 18367027] and Cilostazol for peripheral arterial occlusive disease [PMID: 18436153], amongst others.
Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction. In rod cells, PDE is oligomeric, comprising an alpha-, a beta- and 2 gamma-subunits, while in cones, PDE is a homodimer of alpha chains, which are associated with several smaller subunits. Both rod and cone PDEs catalyse the hydrolysis of cAMP or cGMP to the corresponding nucleoside 5' monophosphates, both enzymes also binding cGMP with high affinity. The cGMP-binding sites are located in the N-terminal half of the protein sequence, while the catalytic core resides in the C-terminal portion.
This entry represents the catalytic domain superfamily of PDE which is multihelical and can be divided into three subdomains.
- G3DSA:1.10.1300.10 (G3DSA:1.10.1300.10)