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332  structures 307  species 1  interaction 2707  sequences 49  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
Identifiers
Symbol PDEase_I
Pfam PF00233
InterPro IPR002073
PROSITE PDOC00116
SCOP 1f0j
SUPERFAMILY 1f0j
CDD cd00077
3',5'-cyclic-nucleotide phosphodiesterase
Identifiers
EC number 3.1.4.17
CAS number 9040-59-9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

3'5'-cyclic nucleotide phosphodiesterases (EC 3.1.4.17, 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:

  • 3',5'-cyclic AMP
  • 3',5'-cyclic dAMP
  • 3',5'-cyclic IMP
  • 3',5'-cyclic GMP
  • 3',5'-cyclic CMP

Function[edit]

Phototransduction[edit]

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[edit]

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]

Structure[edit]

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.

Examples[edit]

Human genes encoding proteins containing this domain include:

References[edit]

  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. ^ 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". Proc. Natl. Acad. Sci. U.S.A. 85 (8): 2424–8. doi:10.1073/pnas.85.8.2424. PMC 280009. PMID 2833739. 
  3. ^ 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". J. Biol. Chem. 264 (8): 4490–7. PMID 2538446. 
  4. ^ 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". Biochem. J. 337 (2): 281–8. PMC 1219963. PMID 9882626. 

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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External database links

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.

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 [PUBMED:18447606], Sildenafil for erectile dysfunction [PUBMED:18367027] and Cilostazol for peripheral arterial occlusive disease [PUBMED:18436153], 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.

This entry represents the catalytic domain of PDE which is multihelical and can be divided into three subdomains.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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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 10 members:

DUF706 HD HD_2 HD_3 HD_4 HD_5 HDOD PDEase_I TraI_2 tRNA_NucTran2_2

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(8)
Full
(2707)
Representative proteomes NCBI
(2650)
Meta
(61)
RP15
(624)
RP35
(791)
RP55
(1167)
RP75
(1579)
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Format an alignment

  Seed
(8)
Full
(2707)
Representative proteomes NCBI
(2650)
Meta
(61)
RP15
(624)
RP35
(791)
RP55
(1167)
RP75
(1579)
Alignment:
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Sequence:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(8)
Full
(2707)
Representative proteomes NCBI
(2650)
Meta
(61)
RP15
(624)
RP35
(791)
RP55
(1167)
RP75
(1579)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

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Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

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Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Prosite
Previous IDs: PDEase;
Type: Domain
Author: Finn RD
Number in seed: 8
Number in full: 2707
Average length of the domain: 218.10 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 32.64 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.8 24.8
Trusted cut-off 24.9 24.8
Noise cut-off 24.4 24.7
Model length: 237
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

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Interactions

There is 1 interaction for this family. More...

PDEase_I

Structures

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 332 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 seqence.

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