A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose.
A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, phosphodiesterase refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many other families of phosphodiesterases, including phospholipases C and D, autotaxin, sphingomyelin phosphodiesterase, DNases, RNases, and restriction endonucleases, as well as numerous less-well-characterized small-molecule phosphodiesterases.
Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system.
3′,5′-cyclic-nucleotide phosphodiesterases (EC 3.1.4.17) are a family of phosphodiesterases. Generally, these enzymes hydrolyze a nucleoside 3′,5′-cyclic phosphate to a nucleoside 5′-phosphate:
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.
Phosphodiesterase 1, PDE1, EC 3.1.4.1, systematic name oligonucleotide 5′-nucleotidohydrolase) is a phosphodiesterase enzyme also known as calcium- and calmodulin-dependent phosphodiesterase. It is one of the 11 families of phosphodiesterase (PDE1-PDE11). Phosphodiesterase 1 has three subtypes, PDE1A, PDE1B and PDE1C which divide further into various isoforms. The various isoforms exhibit different affinities for cAMP and cGMP.
The PDE2 enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs can be subdivided to 11 families. The different PDEs of the same family are functionally related despite the fact that their amino acid sequences show considerable divergence. The PDEs have different substrate specificities. Some are cAMP selective hydrolases, others are cGMP selective hydrolases and the rest can hydrolyse both cAMP and cGMP.
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the PDE6B gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness.
cAMP-specific 3',5'-cyclic phosphodiesterase 4C is an enzyme that in humans is encoded by the PDE4C gene.
High affinity cGMP-specific 3',5'-cyclic phosphodiesterase 9A is an enzyme that in humans is encoded by the PDE9A gene.
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.
Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B is an enzyme that in humans is encoded by the PDE1B gene.
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8B is an enzyme that in humans is encoded by the PDE8B gene.
High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A is an enzyme that in humans is encoded by the PDE8A gene. Work by Sebastiaan Bol et al. showed that 5 different transcript variants and their corresponding isoforms are expressed in human macrophages, and suggests that this protein may be required by HIV-1 for its replication.
cGMP-dependent 3',5'-cyclic phosphodiesterase is an enzyme that in humans is encoded by the PDE2A gene.
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' is an enzyme that in humans is encoded by the PDE6C gene.
The GAF domain is a type of protein domain that is found in a wide range of proteins from all species. The GAF domain is named after some of the proteins it is found in: cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. The first structure of a GAF domain solved by Ho and colleagues showed that this domain shared a similar fold with the PAS domain. In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 which bind cGMP to the GAF domain, PDE10 which binds cAMP, and PDE11 which binds both cGMP and cAMP.
Phosphodiesterases (PDEs) are a superfamily of enzymes. This superfamily is further classified into 11 families, PDE1 - PDE11, on the basis of regulatory properties, amino acid sequences, substrate specificities, pharmacological properties and tissue distribution. Their function is to degrade intracellular second messengers such as cyclic adenine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) which leads to several biological processes like effect on intracellular calcium level by the Ca2+ pathway.
Cyclic di-AMP is a second messenger used in signal transduction in bacteria and archaea. It is present in many Gram-positive bacteria, some Gram-negative species, and archaea of the phylum euryarchaeota.
PDE7B is a mammalian gene that encodes a 3'5'-cyclic nucleotide phosphodiesterase (PDE) that converts 3'5'-cyclic adenosine monophosphate (cAMP) to 5'AMP as part of cyclic nucleotide signaling pathways. There are 21 PDE genes in mammals that are pharmacologically-grouped into 11 families based on their biochemical characteristics and sequence conservation. The PDE7 family is composed of PDEs encoded by two genes, PDE7A and PDE7B. These PDEs are highly specific for cAMP relative to cGMP.
