| Primary Identifier | IPR057304 | Type | Domain |
| Short Name | PDE8-like_REC_N |
| description | This domain is found at the N-terminal of high affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8 (PDE8), PDE8A, and PDE8B, which are mainly found in vertebrates. PDE8A hydrolyses the second messenger cAMP, a key regulator of many important physiological processes []. This domain is predicted to adopt a Rossmann fold similar to CheY-type chemotaxis response regulators. This domain is also called REC domain [, ].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 [], Sildenafil for erectile dysfunction []and Cilostazol for peripheral arterial occlusive disease [], 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. |
