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IPR036971

3'5'-cyclic nucleotide phosphodiesterase, catalytic domain superfamily

InterPro entry
Short namePDEase_catalytic_dom_sf
Overlapping entries
 

Description

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
[3]
, Sildenafil for erectile dysfunction
[2]
and Cilostazol for peripheral arterial occlusive disease
[1]
, amongst others.

Retinal 3',5'-cGMP phosphodiesterase is located in photoreceptor outer segments: it is light activated, playing a pivotal role in signal transduction
[4]
. 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 C-terminal catalytic domain superfamily of PDE which is multihelical and can be divided into three subdomains.

References

1.Type 3 phosphodiesterase inhibitors may be protective against cerebrovascular events in patients with claudication. Stone WM, Demaerschalk BM, Fowl RJ, Money SR. 17, 129-33, (2008). View articlePMID: 18436153

2.Phosphodiesterase 5 inhibition in essential hypertension. Ghiadoni L, Versari D, Taddei S. Curr. Hypertens. Rep. 10, 52-7, (2008). View articlePMID: 18367027

3.Roflumilast: an oral, once-daily selective PDE-4 inhibitor for the management of COPD and asthma. Field SK. 17, 811-8, (2008). View articlePMID: 18447606

4.Photoreceptor Phosphodiesterase (PDE6): Structure, Regulatory Mechanisms, and Implications for Treatment of Retinal Diseases. Cote RH, Gupta R, Irwin MJ, Wang X. Adv Exp Med Biol 1371, 33-59, (2022). View articlePMID: 34170501

GO terms

Cross References

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