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900  structures 1277  species 0  interactions 15529  sequences 173  architectures

Family: PDEase_I (PF00233)

Summary: 3'5'-cyclic nucleotide phosphodiesterase

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This is the Wikipedia entry entitled "Cyclic nucleotide phosphodiesterase". More...

Cyclic nucleotide phosphodiesterase Edit Wikipedia article

3',5'-cyclic nucleotide phosphodiesterase
Phosphodiesterase 4D hexamer, Human
3',5'-cyclic-nucleotide phosphodiesterase
EC number3.1.4.17
CAS number9040-59-9
IntEnzIntEnz view
ExPASyNiceZyme view
MetaCycmetabolic pathway
PDB structuresRCSB PDB PDBe PDBsum
Gene OntologyAmiGO / QuickGO

3'5'-cyclic nucleotide phosphodiesterases are a family of phosphodiesterases. Generally, these enzymes hydrolyze some nucleoside 3',5'-cyclic phosphate to some nucleoside 5'-phosphate thus controlling the cellular levels of the cyclic second messengers and the rates of their degradation.[1] Some examples of nucleoside 3',5'-cyclic phosphate include:

There are 11 distinct phosphodiesterase families (PDE1–PDE11) with a variety in isoforms and splicing having unique three-dimensional structure, kinetic properties, modes of regulation, intracellular localization, cellular expression, and inhibitor sensitivities.[1]


The systematic for this enzyme is 3',5'-cyclic-nucleotide 5'-nucleotidohydrolase. Other names in use include cyclic 3',5'-mononucleotide phosphodiesterase, PDE, cyclic 3',5'-nucleotide phosphodiesterase, cyclic 3',5'-phosphodiesterase, 3',5'-nucleotide phosphodiesterase, 3':5'-cyclic nucleotide 5'-nucleotidohydrolase, 3',5'-cyclonucleotide phosphodiesterase, 3', 5'-cyclic nucleoside monophosphate phosphodiesterase, 3': 5'-monophosphate phosphodiesterase (cyclic CMP), cytidine 3':5'-monophosphate phosphodiesterase (cyclic CMP), cyclic 3',5-nucleotide monophosphate phosphodiesterase, nucleoside 3',5'-cyclic phosphate diesterase, nucleoside-3',5-monophosphate phosphodiesterase)



Retinal 3',5'-cGMP phosphodiesterase (PDE) is located in photoreceptor outer segments and is an important enzyme in phototransduction.[2]

PDE in rod cells are oligomeric, made up of two heavy catalytic subunits, α (90 kDa) and β (85 kDa,) and two lighter inhibitory γ subunits (11 kDa each).[3][4]

PDE in rod cells are activated by transducin. Transducin is a G protein which upon GDP/GTP exchange in the transducin α subunit catalyzed by photolyzed rhodopsin. The transducin α subunit (Tα) is released from the β and γ complex and diffuses into the cytoplasmic solution to interact and activate PDE.

Activation by Tα

There are two proposed mechanisms for the activation of PDE. The first proposes that the two inhibitory subunits are differentially bound, sequentially removable and exchangeable between the native complex PDEαβγ2 and PDEαβ. GTP-bound-Tα removes the inhibitory γ subunits one at a time from the αβ catalytic subunits.[3] The second and more likely mechanism states that the GTP-Tα complex binds to the γ subunits but rather than dissociating from the catalytic subunits, it stays with the PDEαβ complex.[5][6] Binding of the GTP-Tα complex to the PDE γ subunits likely causes a conformational shift in the PDE, allowing better access to the site of cGMP hydrolysis on PDEαβ.[5]


The binding site for PDE α and β subunits are likely to be in the central region of the PDE γ subunits [4]. The C-terminal of the PDE γ subunit is likely to be involved in inhibition of PDE α and β subunits, the binding site for Tα and GTPase accelerating activity for the GTP-bound Tα.[6]

In cones, PDE is a homodimer of alpha chains, associated with several smaller subunits. Both rod and cone PDEs catalyze the hydrolysis of cAMP or cGMP to their 5' monophosphate form. Both enzymes also bind 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.


Human genes encoding proteins containing this domain include:


  1. ^ a b Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacological Reviews. 58 (3): 488–520. doi:10.1124/pr.58.3.5. PMID 16968949.
  2. ^ Arkinstall S, Watson SP (1994). "Opsins". The G-protein linked receptor factsbook. Boston: Academic Press. pp. 214–222. ISBN 978-0-12-738440-5.
  3. ^ a b Deterre P, Bigay J, Forquet F, Robert M, Chabre M (April 1988). "cGMP phosphodiesterase of retinal rods is regulated by two inhibitory subunits". Proceedings of the National Academy of Sciences of the United States of America. 85 (8): 2424–8. doi:10.1073/pnas.85.8.2424. PMC 280009. PMID 2833739.
  4. ^ a b Kovacik, Lubomir; Stahlberg, Henning; Engel, Andreas; Palczewski, Krzysztof; Gulati, Sahil (2019-02-01). "Cryo-EM structure of phosphodiesterase 6 reveals insights into the allosteric regulation of type I phosphodiesterases". Science Advances. 5 (2): eaav4322. doi:10.1126/sciadv.aav4322. ISSN 2375-2548. PMC 6392808.
  5. ^ a b Kroll S, Phillips WJ, Cerione RA (March 1989). "The regulation of the cyclic GMP phosphodiesterase by the GDP-bound form of the alpha subunit of transducin". The Journal of Biological Chemistry. 264 (8): 4490–7. PMID 2538446.
  6. ^ a b Liu Y, Arshavsky VY, Ruoho AE (January 1999). "Interaction sites of the C-terminal region of the cGMP phosphodiesterase inhibitory subunit with the GDP-bound transducin alpha-subunit". The Biochemical Journal. 337 (2): 281–8. doi:10.1042/0264-6021:3370281. PMC 1219963. PMID 9882626.
This article incorporates text from the public domain Pfam and InterPro: IPR002073

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This tab holds annotation information from the InterPro database.

InterPro entry IPR002073

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.

All of these forms contain a catalytic domain of approximately 270 amino acids at the carboxyl terminus. Regulatory domains that vary widely among the PDEase subfamilies flank the catalytic core and include regions that autoinhibit the catalytic domains as well as targeting sequences that control subcellular localization [ PUBMED:15260978 ].

PDEase catalytic domains adopt a compact alpha-helical structure consisting of 16 alpha-helices that can be divided into three subdomains. The active site of PDEases is a deep pocket formed by the tree subdomains and can be divided into two major subpockets for binding of divalent metals and substrate/inhibitors, respectively. The active site of all PDEase domains contains two divalent metal ions: zinc and probably magnesium [ PUBMED:15260978 , PUBMED:10846163 , PUBMED:17305581 ].

Gene Ontology

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Domain organisation

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Pfam Clan

This family is a member of clan HD_PDEase (CL0237), which has the following description:

This clan includes a range of phosphohydrolase enzymes with a common helical fold.

The clan contains the following 13 members:

DUF4202 HD HD_2 HD_3 HD_4 HD_5 HD_6 HDOD MIOX PDEase_I SidE_PDE TraI_2 tRNA_NucTran2_2


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Seed source: Prosite
Previous IDs: PDEase;
Type: Domain
Sequence Ontology: SO:0000417
Author: Finn RD
Number in seed: 255
Number in full: 15529
Average length of the domain: 225.60 aa
Average identity of full alignment: 34 %
Average coverage of the sequence by the domain: 32.93 %

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HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.8 24.8
Trusted cut-off 24.8 24.9
Noise cut-off 24.7 24.7
Model length: 232
Family (HMM) version: 21
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PDEase_I domain has been found. There are 900 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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