Cyclic nucleotide phosphodiesterase

3',5'-cyclic nucleotide phosphodiesterase

Phosphodiesterase 4D hexamer, Human
Symbol PDEase_I
Pfam PF00233
InterPro IPR002073
SCOP 1f0j
CDD cd00077
3',5'-cyclic-nucleotide phosphodiesterase
EC number
CAS number 9040-59-9
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

3'5'-cyclic nucleotide phosphodiesterases (EC, 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) are a family of phosphodiesterases. Generally, these enzymes hydrolyze some nucleoside 3’,5’-cyclic phosphate to some nucleoside 5’-phosphate. Some examples of nucleoside 3’,5’-cyclic phosphate include:



Retinal 3',5'-cGMP phosphodiesterase (PDE) is located in photoreceptor outer segments and is an important enzyme in phototransduction.[1]

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).[2]

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 inihibitory γ subunits one at a time from the αβ catalytic subunits.[2] 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.[3][4] 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.[3]


The binding site for PDE α and β subunits are likely to be in the central region of the PDE γ subunits. 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.[4]

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. Arkinstall S, Watson SP (1994). "Opsins". The G-protein linked receptor factsbook. Boston: Academic Press. pp. 214–222. ISBN 0-12-738440-5.
  2. 1 2 Deterre P, Bigay J, Forquet F, Robert M, Chabre M (April 1988). "cGMP phosphodiesterase of retinal rods is regulated by two inhibitory subunits". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2424–8. doi:10.1073/pnas.85.8.2424. PMC 280009Freely accessible. PMID 2833739.
  3. 1 2 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". J. Biol. Chem. 264 (8): 4490–7. PMID 2538446.
  4. 1 2 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". Biochem. J. 337 (2): 281–8. doi:10.1042/0264-6021:3370281. PMC 1219963Freely accessible. PMID 9882626.

This article incorporates text from the public domain Pfam and InterPro IPR002073

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