Information on EC 3.1.4.53 - 3',5'-cyclic-AMP phosphodiesterase

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The expected taxonomic range for this enzyme is: Eukaryota, Bacteria

EC NUMBER
COMMENTARY
3.1.4.53
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-AMP phosphodiesterase
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
adenosine 3',5'-cyclic phosphate + H2O = AMP
show the reaction diagram
-
-
-
-
adenosine 3',5'-cyclic phosphate + H2O = AMP
show the reaction diagram
catalytic reaction mechanism, overview
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-AMP 5'-nucleotidohydrolase
Requires Mg2+ or Mn2+ for activity [2]. This enzyme is specific for 3',5'-cAMP and does not hydrolyse other nucleoside 3',5'-cyclic phosphates such as cGMP (cf. EC 3.1.4.17, 3,5-cyclic-nucleotide phosphodiesterase and EC 3.1.4.35, 3,5-cyclic-GMP phosphodiesterase). It is involved in modulation of the levels of cAMP, which is a mediator in the processes of cell transformation and proliferation [3].
CAS REGISTRY NUMBER
COMMENTARY
9036-21-9
-
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
calmodulin-dependent cAMP-phosphodiesterase, commercial product
-
-
Manually annotated by BRENDA team
isoform PDE4
-
-
Manually annotated by BRENDA team
; isoform PDE4, enzyme is expressed during single cell stages and expression increases after 9 h of starvation
SwissProt
Manually annotated by BRENDA team
isoform PDE4
-
-
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
; isoform PDE4
-
-
Manually annotated by BRENDA team
; isoform PDE4A8
SwissProt
Manually annotated by BRENDA team
isoform PDE4A10
SwissProt
Manually annotated by BRENDA team
isoform PDE4B2B; isoform PDE4C2
-
-
Manually annotated by BRENDA team
isoform PDE4B5, variant of PDE4B with a different 5'-terminus
SwissProt
Manually annotated by BRENDA team
isoform PDE4D2
SwissProt
Manually annotated by BRENDA team
isoform PDE4D2
-
-
Manually annotated by BRENDA team
isoform PDE4D5
-
-
Manually annotated by BRENDA team
isoforms PDE4D3 and PDE4D5
-
-
Manually annotated by BRENDA team
patients with idiopathic pulmonary arterial hypertension or secondary pulmonary hypertension
-
-
Manually annotated by BRENDA team
PDE4; PDE7; PDE8
-
-
Manually annotated by BRENDA team
PDE4A
SwissProt
Manually annotated by BRENDA team
PDE4B
SwissProt
Manually annotated by BRENDA team
PDE4C
SwissProt
Manually annotated by BRENDA team
PDE4D
SwissProt
Manually annotated by BRENDA team
PDE7A
UniProt
Manually annotated by BRENDA team
PDE7A, recombinant protein, N-terminally truncated
-
-
Manually annotated by BRENDA team
PDE7A; PDE7A2
UniProt
Manually annotated by BRENDA team
PDE7B
SwissProt
Manually annotated by BRENDA team
PDE8A
SwissProt
Manually annotated by BRENDA team
PDE8B
SwissProt
Manually annotated by BRENDA team
PdeH; enzymes PDEH and PDEL
UniProt
Manually annotated by BRENDA team
PdeL; enzyme PDEL
UniProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
-
SwissProt
Manually annotated by BRENDA team
; isoform PDE7A1
-
-
Manually annotated by BRENDA team
isoform PDE4
-
-
Manually annotated by BRENDA team
plasmodium stage
-
-
Manually annotated by BRENDA team
gene cpdA; strain PAK
UniProt
Manually annotated by BRENDA team
; isoform PDE4D, short variants PDE4D1 and PDE4D2 are transcriptionally regulated by follicle-stimulating hormone
-
-
Manually annotated by BRENDA team
male Sprague-Dawley
-
-
Manually annotated by BRENDA team
Sprague-Dawley, male
SwissProt
Manually annotated by BRENDA team
isoform PDEB2
SwissProt
Manually annotated by BRENDA team
; isoform PDEA1
SwissProt
Manually annotated by BRENDA team
; isoform PDEB1, expression in all developmental stages
SwissProt
Manually annotated by BRENDA team
isoform PDEB2, expression in all developmental stages
-
-
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
D4P095
deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of Pseudomonas aeruginosa virulence traits
malfunction
-
PDE4 inhibition together with transforming growth factor-beta1 results in augmented PGE2 production together with increased expression of COX mRNA and protein. inhibitors may attenuate fibroblast activities that can lead to fibrosis, PDE4 inhibitors may be particularly effective in the presence of transforming growth factor-beta1-induced fibroblast stimulation
malfunction
D0ERY7, D0ERY8
a pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
malfunction
D4P095
deletion of cpdA results in the accumulation of intracellular cAMP and altered regulation of Pseudomonas aeruginosa virulence traits. The cpdA mutant has a cAMP-independent small-colony, slow-growth phenotype
malfunction
-
effects of acute hypoxia on cAMP accumulation induced by PDE inhibitors in oxygen-specific chemosensors, the carotid bodies and in non-chemosensitive CB-related structures: carotid arteries and superior cervical ganglia, overview. Acute hypoxia enhances the effects of IBMX and PDE4 inhibitors on cAMP accumulation in carotid arteries and bodies, while in superior cervical ganglia In SCG, acute hypoxia reduces cAMP accumulation induced by all the four PDE inhibitors
malfunction
D0ERY7, D0ERY8
loss of PdeH leads to increased accumulation of intracellular cAMP during vegetative and infectious growth. Furthermore, the pdeHD shows 2-3fold enhanced conidiation, precocious appressorial development, loss of surface dependency during pathogenesis, and highly reduced in planta growth and host colonization. A pdeHDELTA/pdeLDELTA mutant shows reduced conidiation, exhibits dramatically increased cAMP levels relative to the wild-type, and is completely defective in virulence
malfunction
-
PDE8B KO mice have elevated levels of urinary corticosterone in both basal and stressed conditions compared with their littermate wild-type controls. PDE8B KO mice exhibit adrenal hypersensitivity toward adrenocorticotropin. PDE8B gene ablation increases mRNA expressions of StAR protein and MC2R
metabolism
-
cyclic AMP-dependent pathways mediate the communication between external stimuli and the intracellular signaling machinery, thereby influencing important aspects of cellular growth, morphogenesis and differentiation. Crucial to proper function and robustness of these signaling cascades is the strict regulation and maintenance of intracellular levels of cAMP through a fine balance between biosynthesis, by adenylate cyclases, and hydrolysis, by cAMP phosphodiesterases
physiological function
D4P095
CpdA is required for cAMP homeostasis and virulence factor regulation, CpdA affects vfr expression and Vfr protein levels and production of virulence factors ExoS, ToxA, and protease IV
physiological function
-
phosphodiesterase 4 contributes to maintenance of retinal vascular tone
physiological function
-
cAMP-specific PDE 4 isoforms underpin compartmentalized cAMP signalling in mammalian cells through targeting to specific signalling complexes. Phosphorylation of PDE4A5 by MK2 confers the amplification of intracellular cAMP accumulation in response to adenylate cyclase activation by attenuating a major desensitization system to cAMP. Long PDE4 isoforms thus provide a novel node for cross-talk between the cAMP and p38 MAPK signalling systems at the level of MK2
physiological function
D4P095
CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro and that it utilizes an iron-dependent catalytic mechanism. The cAMP-dependent transcription factor Vfr directly regulates cpdA expression in response to intracellular cAMP accumulation, thus providing a feedback mechanism for controlling cAMP levels and fine-tuning virulence factor expression. CpdA affects vfr expression and Vfr protein levels. CpdA affects production of virulence factors ExoS, ToxA, and protease IV
physiological function
D0ERY7, D0ERY8
expendable PdeL function
physiological function
-
importance of PDE8s in cAMP regulation of steroid production. PDE8A plays an important role in regulating a pool of cAMP that promotes testicular steroidogenesis. PDE8B regulates adrenocorticotropin-stimulated AZF steroidogenesis by both short- and long-term mechanisms
physiological function
-
in cardiac myocytes coupling of PDE4 members to the beta2 adrenergic receptor regulates several aspects of beta2 adrenergic signaling. Inhibition of PDE4 increases cAMP in response to activation of beta2 adrenergic receptors, but has no effect on beta1 adrenergic signaling, demonstrating the selectivity of PDE association. Recruitment of PDE4 to the beta2 adrenergic receptor allows PDE4 to act locally and hydrolyze cAMP produced in response to activation of this receptor, modulating its downstream effects. PDE4 activation is regulated via phosphorylation by PKA in the UCR or phosphorylation by ERK in the C-terminus, depending on the individual isoform. The regulated release of ATP from erythrocytes occurs via a defined signaling pathway and requires increases in cAMP. It is well recognized that cAMP is a critical second messenger in diverse signaling pathways. In all cells increases in cAMP are localized and regulated by the activity of phosphodiesterases, PDEs. The subcellular localization of PDEs is recognized to be a key mechanism for compartmentalization of cyclic nucleotide signaling. PDEs within these cells regulate the compartmentalization of cAMP signaling allowing for specific cell responses. The subcellular location of PDEs is critical for coupling these enzymes to specific signal transduction pathways, which permit specific PDEs to regulate local increases in cAMP produced by activation of ligand specific receptor
physiological function
-
PDE4D regulates both the activity and subcellular localization of EPAC1, mechanism for regulated EPAC1 signaling in these cells, overview
physiological function
D0ERY7, D0ERY8
PDEH is necessary for proper aerial hyphal growth. PdeH-dependent biphasic regulation of cAMP levels during early and late stages of appressorial development. PdeH-mediated sustainance and dynamic regulation of cAMP signaling during Magnaporthe oryzae development is crucial for successful establishment and spread of the blast disease in rice. The PdeH activity is a key regulator of asexual and pathogenic development in Magnaporthe oryzae
physiological function
-
the autocrine production of cAMP and extracellular cAMP-specific phosphodiesterase is an important constituent of the mechanism controlling the motile behavior of the plasmodium
physiological function
-
the PDE4-catalyzed hydrolysis of cAMP consists of two reaction stages: cAMP hydrolysis and bridging hydroxide ion regeneration. The stage 1 includes the binding of cAMP in the active site, nucleophilic attack of the bridging hydroxide ion on the phosphorus atom of cAMP, cleavage of O3'-P phosphoesteric bond of cAMP, protonation of the departing O3' atom, and dissociation of hydrolysis product, AMP. The stage 2 includes the binding of solvent water molecules with the metal ions in the active site and regeneration of the bridging hydroxide ion. The dissociation of the hydrolysis product is found to be rate-determining for the enzymatic reaction process
physiological function
-
constitutive signaling of the overexpressed HA-tagged 5-hydroxytryptamine4(b) receptor in HEK293 cells is regulated predominantly by cAMP-specific phosphodiesterase PDE4,with a secondary role for dual specific phosphodiesterase PDE3 that is unmasked in the presence of PDE4 inhibition. Overexpressed PDE4D3 and PDE3A1, and to a smaller extent PDE4D5 co-immunoprecipitate constitutively with the 5-hydroxytryptamine4(b) receptor. Phosphodiesterase activity measurements in immunoprecipitates of the 5-hydroxytryptamine4(b) receptor confirm the association of PDE4D3 with the receptor and provide evidence that the activity of this phophodiesterase may be increased upon receptor stimulation with 5-hydroxytryptamine
physiological function
-
isoform PDE4B is involved in beta-adrenergic signaling in the heart. Genetic ablation of PDE4B disrupts beta-adrenergic signaling-induced cAMP transients at the sarcolemma but not in the bulk cytosol of cardiomyocytes. PDE4B regulates beta1-adrenergic signaling-, but not beta2-adrenergic signaling- or PGE2-induced responses. PDE4B shows selective effects on protein kinase A-mediated phosphorylation patterns. PDE4B limits the proein kinase A-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca2+ channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. beta1-Adrenergic signaling- but not beta2-adrenergic signaling-ligation induced protein kinase A-dependent activation of PDE4B and interruption of this negative feedback with protein kinase A inhibitors increase sarcolemmal cAMP
physiological function
Q23917
mutation in cAMP-specific phosphodiesterase RegA in cells lacking either G protein Galpha2 or Galpha4 subunits has no major effects on developmental morphology but enriches the distribution of the Galpha mutant cells to the prespore/prestalk border in chimeric aggregates. The loss of RegA function has no effect on Galpha4-mediated folate chemotaxis. The RegA gene disruption in cells lacking Galpha4 results in a substantial rescue and acceleration of spore production. This rescue in sporulation requires cell autonomous signaling. Intercellular signals from strains lacking RegA increase the expression of the prestalk gene ecmB and accelerate the vacuolization of stalk cells. Intercellular signaling from the strain lacking both Galpha4 and RegA do not induce ecmA gene expression indicating cell-type specificity in the promotion of prestalk cell development. RegA gene disruption in a Galpha4 overexpression strain does not result in precocious sporulation or stalk cell development
physiological function
-
phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation
metabolism
-
PKA, EPAC1, and PDE4D differentially regulate humanarterial endothelial cell vascular endothelial cadherin-based structures, overview. Protein-protein interactions between EPAC1 and PDE4D serve to foster their integration into vascular endothelial cadherin-based complexes and allow robust local regulation of EPAC1-based stabilization of vascular endothelial cadherin-based adhesions
additional information
-
PDE4 is a cAMP-specific PDE which has four subfamilies, A thru D, that include over 50 isoforms
SUBSTRATE
PRODUCT                      
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-O-(N-methylanthraniloyl)adenosine-3',5'-cyclic monophosphate + H2O
2'-O-(N-methylanthraniloyl)adenosine-5'-monophosphate
show the reaction diagram
Q49UB9
fluorescent cAMP analogue
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
O95263
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q86H13
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q4ZHU6
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q07343
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
B1PSD9
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q846Z1
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
specific substrate
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
P27815, Q07343, Q08493, Q08499, Q13946
specific substrate
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q86H13
DdPDE4 regulates intercellular cAMP during multicellular development
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
activity with 3',5'-cAMP is much higher than activity with 3',5'-cGMP, PDE7
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q6S996, Q6S997
LmjPDEB1 is completely cAMP-specific
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q6S996, Q6S997
LmjPDEB2 is completely cAMP-specific
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
specific for 3',5'-cAMP, PDE4, specific for 3',5'-cAMP, PDE8
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
specific for cAMP
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
P27815, Q07343, Q08493, Q08499, Q13946
PDE4 hydrolyses selectively 3',5'-cAMP with high affinity
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
D4P095
CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro
-
-
?
3',5'-cAMP + H2O
adenosine 5'-phosphate
show the reaction diagram
-
PDE4, PDE7
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
-
activity with 3',5'-cAMP is much higher than activity with 3',5'-cGMP, PDE7
-
-
?
3',5'-cGMP + H2O
5'-AMP
show the reaction diagram
-
low activity
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q49UB9
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q86H13
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P54748
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P14646
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
O89084, Q9QXI7
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
O60658
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q9QXQ1
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q9GQU6
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q9NP56
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q6XG56
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
D4P095
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
D0ERY7, D0ERY8
-
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q86H13
DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P14646
PDE4B4 isoform may have a distinct functional role in regulating cAMP levels in specific cell types
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
attenuation of the activity of the cAMP-specific phosphodiesterase PDE4A5 by interaction with the immunophilin XAP2
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q309F4
no activity with cGMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P70453
no activity with cGMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
O88502
PDE8 is specific for the hydrolysis of cAMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
the enzyme is highly specific for cAMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
the enzyme is specific for cAMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
the enzyme is specific for cAMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q4ZHU6
the enzyme is specific fpr cAMP
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
both PDE8A and 8B hydrolyze cAMP with a very high affinity
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
determination of reaction rate and mechanism using computational modeling, quantum mechanical/molecular mechanical-free energy perturbation, QM/MM-FE, and QM/MM-Poisson-Boltzmann surface area, PBSA, calculations. The onQM/MMreaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system identifies a unique catalytic reaction mechanism, overview
-
-
?
cAMP + H2O
AMP
show the reaction diagram
-
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
P27815, Q08499
-
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
Q49UB9
-
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
Q309F4
-
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
-
degradation of extracellular cAMP
-
-
?
cAMP + H2O
5'-AMP
show the reaction diagram
-
isoform PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
P27815, Q08499
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
O60658
-
-
-
?
additional information
?
-
-
during development PDE4 is the major PDE
-
-
-
additional information
?
-
-
PDE4 is a component of signaling pathways involved in the mediation of antidepressant activity
-
-
-
additional information
?
-
-
PDE4 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
-
-
-
additional information
?
-
-
PDE4B is involved in LPS signaling
-
-
-
additional information
?
-
-
enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
-
-
-
additional information
?
-
-
isoform PDE4 regulates both GalphaS-dependent and GalphaS-indeoendent cAMP pools in the neurons controling locomotion rate
-
-
-
additional information
?
-
Q86H13
cGMP is hydrolyzed at least 100fold more slowly than cAMP
-
-
-
additional information
?
-
Q309F4
cGMP neither activates the enzyme nor competes as a substrate
-
-
-
additional information
?
-
-
almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH
-
-
-
additional information
?
-
Q08499
interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
-
-
-
additional information
?
-
-
PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
-
-
-
additional information
?
-
-
PDE4D5 plays a nonredundant and functionally significant role in its interaction with beta-arrestin and in the mechanics of beta2-adrenergic receptor signalling
-
-
-
additional information
?
-
-
PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of the C subunit of the cAMP-dependent kinase
-
-
-
additional information
?
-
Q38F42, Q38F46, Q8WQX9
TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
-
-
-
additional information
?
-
-
no activity with cGMP
-
-
-
additional information
?
-
Q4ZHU6
no activity with cGMP
-
-
-
additional information
?
-
Q49UB9
no activity with up to 0.1 mM cGMP
-
-
-
additional information
?
-
-
no hydrolysis of cGMP
-
-
-
additional information
?
-
Q9QXQ1
PDE7B does not hydrolyse cGMP
-
-
-
additional information
?
-
Q9NP56
PDE7B does not hydrolyse cGMP
-
-
-
additional information
?
-
-
wild-type enzyme shows no activity with cGMP, mutant enzymes D440N and D440A show activity with cGMP
-
-
-
additional information
?
-
-
increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl salt-sensitive rat
-
-
-
additional information
?
-
-
PDE4 regulates adenosine A2A receptor signaling in striatopallidal neurons
-
-
-
additional information
?
-
-
Myxococcus xanthus PdeA and PdeB, enzymes hydrolyze 3',5'- and 2',3'-cyclic AMP to adenosine, and also demonstrate phosphatase activity toward nucleoside 5'-tri-, 5'-di-, 5'- and 3'-monophosphates with highest activities for nucleoside 5'-monophosphates. PdeA and PdeB also show high phosphomonoesterase activities against 50-UMP, 3'-AMP, and 3'-GMP, low activities against 5'-dAMP, and no activities toward 2'-AMP and 2'-GMP
-
-
-
additional information
?
-
D4P095
iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
-
-
-
additional information
?
-
-
protein-protein interactions between EPAC1 and PDE4D, peptide mapping for binding site determination. A cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters vascular endothelial cell permeability
-
-
-
additional information
?
-
-
recruitment of PDE4 to the beta2 adrenergic receptor
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
LITERATURE
(Substrate)
COMMENTARY
(Product)
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
-
the reaction product, 5'-AMP, is further dephosphorylated to adenosine by PdeA and PdeB
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
Q86H13
DdPDE4 regulates intercellular cAMP during multicellular development
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
-
PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of C subunit of cAMP-dependent protein kinase
-
-
?
3',5'-cAMP + H2O
5'-AMP
show the reaction diagram
D4P095
CpdA possesses 3',5'-cAMP phosphodiesterase activity in vitro
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
Q86H13
DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
P14646
PDE4B4 isoform may have a distinct functional role in regulating cAMP levels in specific cell types
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
both PDE8A and 8B hydrolyze cAMP with a very high affinity
-
-
?
adenosine 3',5'-cyclic phosphate + H2O
adenosine 5'-phosphate
show the reaction diagram
-
determination of reaction rate and mechanism using computational modeling, quantum mechanical/molecular mechanical-free energy perturbation, QM/MM-FE, and QM/MM-Poisson-Boltzmann surface area, PBSA, calculations. The onQM/MMreaction-coordinate calculations including the protein environment of any PDE-catalyzed reaction system identifies a unique catalytic reaction mechanism, overview
-
-
?
additional information
?
-
-
during development PDE4 is the major PDE
-
-
-
additional information
?
-
-
PDE4 is a component of signaling pathways involved in the mediation of antidepressant activity
-
-
-
additional information
?
-
-
PDE4 may be involved in the cyclic nucleotide-mediated control of smooth muscle tone
-
-
-
additional information
?
-
-
PDE4B is involved in LPS signaling
-
-
-
additional information
?
-
-
enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
-
-
-
additional information
?
-
-
isoform PDE4 regulates both GalphaS-dependent and GalphaS-indeoendent cAMP pools in the neurons controling locomotion rate
-
-
-
additional information
?
-
-
almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH
-
-
-
additional information
?
-
Q08499
interaction of PDE4D5 with both the N- and C-domains of beta-arrestin 2 are essential for beta2-adrenoceptor regulation
-
-
-
additional information
?
-
-
PDE4D deficiency may contribute to heart failure and arrhythmias by promoting defective regulation of the RyR2 channel in humans
-
-
-
additional information
?
-
-
PDE4D5 plays a nonredundant and functionally significant role in its interaction with beta-arrestin and in the mechanics of beta2-adrenergic receptor signalling
-
-
-
additional information
?
-
-
PDE7A1 possesses a non-catalytic activity that can contribute to the termination of cAMP signals via direct inhibition of the C subunit of the cAMP-dependent kinase
-
-
-
additional information
?
-
Q38F42, Q38F46, Q8WQX9
TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs
-
-
-
additional information
?
-
-
increased PDE4 activity, specifically phosphodiesterase 4B4 activity, reduces beta-adrenergic signaling in the kidney and contributes to salt-sensitive hypertension in the Dahl salt-sensitive rat
-
-
-
additional information
?
-
-
PDE4 regulates adenosine A2A receptor signaling in striatopallidal neurons
-
-
-
additional information
?
-
-
Myxococcus xanthus PdeA and PdeB, enzymes hydrolyze 3',5'- and 2',3'-cyclic AMP to adenosine, and also demonstrate phosphatase activity toward nucleoside 5'-tri-, 5'-di-, 5'- and 3'-monophosphates with highest activities for nucleoside 5'-monophosphates. PdeA and PdeB also show high phosphomonoesterase activities against 50-UMP, 3'-AMP, and 3'-GMP, low activities against 5'-dAMP, and no activities toward 2'-AMP and 2'-GMP
-
-
-
additional information
?
-
D4P095
iron and conserved residues are essential for CpdA activity, the catalytic mechanism for Pseudomonas aeruginosa CpdA utilizes a Fe3+-Fe2+ center
-
-
-
additional information
?
-
-
protein-protein interactions between EPAC1 and PDE4D, peptide mapping for binding site determination. A cell-permeable variant of this peptide antagonizes EPAC1-PDE4D binding and directly alters vascular endothelial cell permeability
-
-
-
additional information
?
-
-
recruitment of PDE4 to the beta2 adrenergic receptor
-
-
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
-
the enzyme is able to use Mg2+, Co2+, and Mn2+, but not Zn2+
Co2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are stimulated 3.2fold and 1.98old, respectively, by 0.05 mM Co2+ at pH 8.0 in 50 mM Tris-HCl buffer
Fe2+
D4P095
Fe2+ is required for enzyme activity. The catalytic mechanism for CpdA utilizes a Fe3+-Fe2+ center. Addition of 0.01 mM FeCl2, as a source of Fe2+, results in an 2fold stimulation of CpdA activity; iron and conserved residues are essential for CpdA activity
Mg2+
Q4ZHU6
required; required
Mg2+
Q309F4
required; required for activity and stability
Mg2+
-
the enzyme requires the presence of at least 1 mM Mn2+ or Mg2+ for maximal activity in vitro
Mg2+
Q6XG56
activity was higher in the presence of Mn2+ than Mg2+ as cofactor
Mg2+
-
the enzyme is able to use Mg2+, Co2+, and Mn2+, but not Zn2+
Mg2+
-
stimulates
Mg2+
-
the concentration-response curve for Mg2+ is biphasic and ranges from 0.1 to 100 mM. Phosphorylation of PDE-4D3 by protein kinase A produces a monophasic Mg2+ response curve
Mn2+
Q4ZHU6
less efficient than Mg2+
Mn2+
-
the enzyme requires the presence of at least 1 mM Mn2+ or Mg2+ for maximal activity in vitro
Mn2+
Q6XG56
activity was higher in the presence of Mn2+ than Mg2+ as cofactor
Mn2+
-
0.015 mM, 20fold increase in activity
Mn2+
-
stimulates
Mn2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are stimulated 4fold and 2.14old, respectively, by 0.05 mM Mn2+ at pH 8.0 in 50 mM Tris-HCl buffer
additional information
Q309F4
no effector: Ca2+, calmodulin
additional information
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are not stimulated by 0.05 mM Ca2+, Mg2+, Fe2+, and Fe3+
additional information
D4P095
no effect on enzyme activity by Mg2+, Mn2+, Zn2+, and Ca2+; the addition of Mg2+, Mn2+, Zn2+, and Ca2+ has no effect on CdpA
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.1195 mM, PDE7
(2E)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
Q6S996, Q6S997
-
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
-
IC50: 0.31 mM, PDE4
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
IC50: 0.00043 mM, PDE4
(4aS,8aR)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
(R)-rolipram
-
-
1,10-phenanthroline
-
0.3 mM, more than 95% inhibition
1-(2,4-dichlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(2-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(3-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(3-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
1-benzyl-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
10-(3-pyrrolidin-1-ylpropyl)-2-(trifluoromethyl)-10H-phenoxazine
-
-
10-(4'-N-morpholinobutyl)-2-chlorophenoxazine
-
-
10-(4'-N-morpholinobutyl)-2-trifluoromethylphenoxazine
-
-
10-(4'-N-piperidinobutyl)-2-chlorophenoxazine
-
-
10-(4'-N-piperidinobutyl)-2-trifluoromethylphenoxazine
-
-
10-(4'-N-pyrrolidinobutyl)-2-chlorophenoxazine
-
-
10-(4'-N-pyrrolidinobutyl)-2-trifluoromethylphenoxazine
-
increase of Km value in presence of inhibitor
10-[3'-[(beta-hydroxyethyl)-piperazino]propyl]-2-trifluoromethylphenoxazine
-
-
10-[30-[(beta-hydroxy ethyl)-piperazino]propyl]-2-chlorophenoxazine
-
-
10-[4'-(N-diethylamino)-butyl]-2-chlorophenoxazine
-
-
10-[4'-(N-diethylamino)butyl]-2-trifluoromethylphenoxazine
-
-
10-[4'-[(beta-hydroxy ethyl)-piperazino]butyl]-2-trifluoro-methylphenoxazine
-
-
10-[4'-[(beta-hydroxy-ethyl)piperazino]butyl]-2-chlorophenoxazine
-
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0203 mM, PDE7; IC50: 0.0453 mM, PDE4
3-(1-methyl-7-oxo-3-propyl-4,7-dihydro-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-4-propoxybenzenesulfonamide
-
-
3-(6-aminopurin-9-yl)nonan-2-ol hydrochloride
-
-
3-isobutyl-1-methyl-xanthine
-
-
3-isobutyl-1-methyl-xanthine
-
-
3-isobutyl-1-methyl-xanthine
-
-
3-isobutyl-1-methylxanthine
-
IC50: 0.007 mM, PDE7
3-isobutyl-1-methylxanthine
-
the inhibitor binds to a subpocket that comprises key residues Ile336, Phe340, Gln369 and Phe372 of PDE54D2. This subpocket may be a common site for binding nonselective inhibitors
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
-
-
3-isobutyl-1-methylxanthine
P70453
;
3-isobutyl-1-methylxanthine
Q9GQU6
-
3-isobutyl-1-methylxanthine
-
nonselective inhibitor, the PDE8A1 catalytic domain is insensitive to 3-isobutyl-1-methylxanthine inhibition
3-isobutyl-1-methylxanthine
-
-
3-isobuytl-1-methylxanthine
-
-
4-(3,4-dimethoxy-phenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
-
PDE4 inhibitor, potent inhibitor of isoform PDE4D3
4-(3,4-dimethoxyphenyl)-2-{5-[(2-{5-[2-(2-fluoro-5-methoxyphenyl)ethyl]tetrahydrofuran-2-yl}ethyl)amino]pentyl}-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
the dual PDE4 inhibitor/selective serotonin reuptake inhibitor shows potent and selective serotonin reuptake inhibition
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
-
Ro20-1724
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
-
Ro-20-1724
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Q13946
-
4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone
-
competitive
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
P27815, Q08499
i.e. NVP; i.e. NVP; i.e. NVP
6-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4,5-dihydropyridazin-3(2H)-one
-
-
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0513 mM, PDE7; IC50: 0.1008 mM, PDE4
8-(4-chlorophenyl)thioguanosine 3',5'-cyclic monophosphate
-
-
8-bromoguanosine 3',5'-cyclic monophosphate
-
-
8-methoxymethyl-isobutylmethylxanthine
-
inhibits activated PDE1 and PDE2 isoforms as well as PDE4 and PDE5
alpha-alpha'-dipyridyl
D4P095
treatment of CpdA with the Fe2+-specific chelator alpha-alpha'-dipyridyl results in a nearly complete loss of activity
apigenin
-
-
apigenin-7-O-glucoside
-
-
apremilast
-
CC-10004, i.e. (S)-N-[2-[1-(3-ethoxy-4-methoxyphenyl)-2-methanesulfonylethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl]acetamide, oral phosphodiesterase-4 inhibitor, apremilast shows no marked selectivity among PDE4 isozymes
avanafil
-
-
AWD 12-250
-
-
AWD 12-281
-
selective PDE4 inhibitor
AWD12-281
-
-
ayanin
-
i.e. quercetin-3,7,4'-O-trimethylether, non-selective phosphodiesterase 1-4 inhibitor
Biochanin A
-
IC50: 0.0085 mM, more selectively inhibits PDE4 than PDE1 or PDE2
BRL-50481
-
PDE7 inhibitor
BRL50481
-
-
Caffeine
-
50 mM, 30% inhibition of soluble enzyme
cAMP-N1-oxide
-
-
cGMP
-
5% inhibition at 0.1 mM
chamomile
-
inhibits cAMP-PDE activity
CI-1044
-
i.e. (R)-N-[9-amino-3,4,6,7-tetrahydro-4-oxo-1-phenylpyrrolo[3,2,1-j,k][1,4] benzodiazepin-3-yl]-3-pyridinecarboxamide, selective inhibitor of PDE4, administration of 160 mg/kg of CI-1044 causes perivascular and interstitial inflammation, with infiltrates of admixed neutrophils and macrophages but without evidence of vascular necrosis, PDE4 inhibitor CI-1044 induces changes of vascular tone that could lead to histological alterations in the mesenteric area
Cibacron blue
-
-
cilomilast
-
-
cilomilast
-
-
Cilostamide
-
IC50: 0.022 mM, PDE7; IC50: 0.0888 mM, PDE4
Cilostamide
-
IC50: 0.099 mM, PDE4
cilostazol
-
IC50: 0.0214 mM, PDE7; IC50: 0.088 mM, PDE4
cis-(+)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-(+)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-(+/-)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-(-)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-(-)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[(E)-4-(1H-imidazol-1-yl)but-2-enyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[2-[2-(1H-imidazol-1-yl)ethoxy]ethyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylmethyl)-benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-2-[4-[(1H-imidazol-1-yl)methyl]benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[2-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[3-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-(piperidin-1-ylmethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-oxopiperidin-1-yl)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(dimethylamino)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
-
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.1.0]hept-4-en-2-one
-
-
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.2.0]oct-4-en-2-one hydrochloride
-
-
D-22888
-
-
DC-TA 46
-
the inhibitor affects memory retention in a visible/hidden-platform water maze task. This memory impairment can be correlated to the decrease of cAMP nucleotide, due to the induction of a PDE4D cAMP-specific PDE isoform
denbufylline
-
-
dexamethasone
-
dexmethasone at 0.1 mg/kg inhibits the activity of PDE4
diazepam
O89084, Q9QXI7
;
dioclein
-
dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 19fold more selective for the activated PDE1 isoform compared to PDE3
diosmetin
-
IC50: 0.0202 mM, PDE4
dipyridamole
Q6S996, Q6S997
-
dipyridamole
-
IC50: 0.013 mM
dipyridamole
Q49UB9
;
dipyridamole
-
-
dipyridamole
-
-
dipyridamole
P70453
;
dipyridamole
Q9GQU6
-
dipyridamole
-
-
dipyridamole
-
inhibits PDE8 at high concentrations
dipyridimole
-
-
E4021
-
-
EDTA
Q4ZHU6
-
EDTA
-
0.3 mM, more than 95% inhibition
EDTA
-
PdeA and PdeB show 39% residual activity, respectively, for 3',5'-cAMP hydrolysis at 0.1 mM EDTA
EHNA
Q49UB9
-
erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride
Q6XG56
-
erythro-9-(2-hydroxy-3-nonyl)adenine
-
7.4% inhibition at 0.1 mM
erythro-9-(2-hydroxy-3-nonyl)adenine
Q49UB9
i.e. EHNA
erythro-9-(2-hydroxy-3-nonyl)adenine
-
a PDE2 selective inhibitor
erythro-9-[3-(2-hydroxynonyl)]-adenine
P70453
-
erythro-9-[3-(2-hydroxynonyl)]adenine
-
0.1 mM, 12% inhibition, wild-type enzyme
etazolate
Q6S996, Q6S997
-
etazolate
-
IC50: 0.025 mM
etazolate
Q4ZHU6
; IC50: 1.3 mM
etazolate
Q9GQU6
-
etazolate
-
-
ethaverine
-
IC50: 0.008 mM
ethyl 2-([4-(3-carbamoylpiperazin-1-yl)-6-[4-(dimethylamino)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[(3,4-dimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-[3-(hydroxymethyl)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-([7-ethyl-6-[(4-sulfamoylbenzyl)amino]-7H-purin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-[[4,6-bis(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 2-[[4-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
-
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00027 mM, PDE4D; IC50: 0.00031 mM, PDE4B
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
-
IC50: 0.017 mM, PDE4B; IC50: 0.019 mM, PDE4D
ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate
-
IC50: 0.015 mM, PDE4B; IC50: 0.019 mM, PDE4D
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00088 mM, PDE4D; IC50: 0.0015 mM, PDE4B
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
-
IC50: 0.06 mM, PDE4B; IC50: 0.082 mM, PDE4D
ethyl 4-methyl-2-([4-(4-methylpiperazin-1-yl)-6-[methyl(3,4,5-trimethoxybenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-(methylamino)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-(piperazin-1-yl)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-([4-[methyl(3,4,5-trimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
-
ethyl 4-methyl-2-[[4-(piperazin-1-yl)-7-(3,4,5-trimethoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1,3-thiazole-5-carboxylate
-
-
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
-
IC50: 0.025 mM, PDE4B; IC50: 0.05 mM, PDE4D
genistein
-
IC50: 0.0095 mM, PDE4
hesperetin
-
IC50: 0.0282 mM, PDE4
hyperoside
-
-
IBMX
B1PSD9
non-selective PDE inhibitor
imperatorin
-
potent PFE4 inhibitor, imperatorin is significantly more active against PDE4B than PDE4A
IR-202
-
PDE7 inhibitor
IR-284
-
dual PDE4/PDE7 inhibitor
isobutylmethylxanthine
O89084, Q9QXI7
0.1 mM, 14% inhibition; 0.1 mM, 32% inhibition
isobutylmethylxanthine
-
a non-specific PDE inhibitor
L-826,141
-
PDE4-selective inhibitor
LAS-31025
-
-
lodenafil
-
-
luteolin
-
IC50: 0.0191 mM, PDE4
luteolin
-
-
luteolin-7-glucoside
-
IC50: 0.043 mM, PDB4, dual inhibitionof PDE2 and PDE4
luteolin-7-O-glucoside
-
-
methylisobutylxanthine
-
-
Milrinone
-
IC50: 0.0175 mM, PDE4; IC50: 0.0583 mM, PDE7
Milrinone
-
42% inhibition at 0.1 mM
Milrinone
Q6S996, Q6S997
-
Milrinone
O89084, Q9QXI7
0.1 mM, 93% inhibition
Milrinone
-
-
mirodenafil
-
-
myricetin
-
IC50: 0.0389 mM, PDE4
N-[2-(5-chloro-2-nitrophenylthio)phenyl]acetamide
Q13946
10% inhibition at 0.01 mM; 11% inhibition at 0.01 mM; lead compound for Parkinson's disease treatment
N-[3-(1H-imidazol-1-yl)propyl]-2-[cis-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2(1H)-yl]acetamide
-
-
N6-Monobutyryl-cAMP
-
-
N6-monobutyyl-cAMP
-
-
O-phospho-L-serine
-
PdeA and PdeB show 59% and 73% residual activity, respectively, for 3',5'-cAMP hydrolysis at 5 mM phosphoserine
O-phospho-L-tyrosine
-
PdeA and PdeB show 44% and 52% residual activity, respectively, for 3',5'-cAMP hydrolysis at 5 mM phosphotyrosine
orthovanadate
-
PdeA and PdeB show 26% and 29% residual activity, respectively, for 3',5'-cAMP hydrolysis at 1 mM orthovanadate
papaverine
Q6S996, Q6S997
-
papaverine
-
IC50: 0.03 mM
papaverine
O88502
-
papaverine
P70453
;
papaverine
Q9GQU6
-
papaverine
-
-
patuletin-7-O-glucoside
-
-
PF-04957325
-
a selective PDE8 inhibitor
prunetin
-
IC50: 0.0114 mM, PDE4
quazinone
-
0.1 mM, 26% inhibition, wild-type enzyme
quercetin
-
IC50: 0.0099 mM, PDE4
quercetin
-
-
quercetin-3,5,7,3',4'-O-pentaacetate
-
-
quercetin-3,5,7,3',4'-O-pentamethylether
-
-
quercetin-3,7,4'-O-trimethylether
-
ayanin
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
-
quercetin-3-O-methylether
-
-
quinazolinamine
-
IC50: 0.34 mM, PDE4
R-rolipram
-
-
Ro 20-1724
O89084, Q9QXI7
0.1 mM, 12% inhibition; 0.1 mM, 4% inhibition
Ro 20-1724
-
selective PDE4 inhibitor
RO 201724
-
-
Ro-20-1724
-
inhibition of PDE4, resulting in increased intacelular cAMP
Ro20-1724
-
-
Ro20-1724
-
PDE4 inhibitor
roflumilast
-
PDE4-selective inhibitor
roflumilast
-
roflumilast is approximately 10fold more potent than rolipram
roflumilast
-
-
roflumilast
-
-
rolipram
-
IC50: 0.00045 mM, PDE4
rolipram
-
18% inhibition at 0.1 mM
rolipram
-
the inhibitor affects memory retention in a visible/hidden-platform water maze task. This memory impairment can be correlated to the decrease of cAMP nucleotide, due to the induction of a PDE4D cAMP-specific PDE isoform
rolipram
Q6S996, Q6S997
-
rolipram
-
IC50: 0.28 mM
rolipram
Q4ZHU6
; IC50: 10.46 mM
rolipram
-
inhibition of PDE4, resulting in increased intacelular cAMP
rolipram
P14646
i.e. 4-[3-(cyclopentoxyl)-4-methoxyphenyl]-2-pyrrolidinone
rolipram
Q6XG56
-
rolipram
O89084, Q9QXI7
0.1 mM, 4% inhibition; 0.1 mM, 7% inhibition
rolipram
-
competitive inhibitor of the cytosol enzyme but as a partial competitive inhibitor of the particulate enzyme. Particulate PDE-46 shows a 60fold higher affinity for rolipram than cytosolic PDE-46
rolipram
-
specific PDE4 inhibitor, complete inhibition at 0.01 mM rolipram
rolipram
-
PDE4 inhibitor
rolipram
-
PDE4 inhibition by rolipram can promote regression of malignant brain tumors when administered as an adjunct to established therapies
rolipram
Q13946
PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram; PDE4 is specifically inhibited by rolipram
rolipram
-
isozyme PDE4A is only partially inhibited by 0.02 mM rolipram, whereas PDE4B is completely inhibited at this concentration
rolipram
-
-
rolipram
-
PDE4-selective inhibitor
rolipram
-
rolipram at 0.3 mg/kg inhibits the activity of PDE4
rolipram
-
PDE4 inhibitor
rolipram
-
Ro 20-1724, a PDE4 selective inhibitor
rolipram
-
a selective inhibitor of PDE4
RP-73401
-
IC50: 0.0000016 mM, PDE4
RPR-73401
-
-
RS-25344
-
phosphorylation of PDE-4D3 increases the sensitivity of the enzyme to inhibition by RS-25344 about 100fold
RS-33793
-
phosphorylation of PDE-4D3 increases the sensitivity of the enzyme to inhibition by RS-33793 about 330fold
SB 207499
-
-
SB 207499
P14270, P14646
-
SCH 351591
-
-
SCH 351591
P14270, P14646
-
SCH51866
-
-
SCH51866
P70453
;
sildenafil
-
IC50: 0.001 mM
sildenafil
-
IC50: 3190 nM, PDE4
sildenafil
-
0.1 mM, 29% inhibition, wild-type enzyme
tadalafil
-
IC50: above 10000 nM, PDE4
tadalafil
-
-
theophylline
-
-
theophylline
-
weak inhibitior
theophylline
-
non-selective inhibitor of phosphodiesterases
trequinsin
-
IC50: 0.0025 mM
trequinsin
Q4ZHU6
-
vardenafil
-
IC50: 2055 nM, PDE4; IC50: 4600 nM, PDE4
vardenafil
-
PDE5 inhibitor
vardenafil
-
-
vinpocetine
-
-
vinpocetine
Q6XG56
-
vinpocetine
-
0.1 mM, 34% inhibition
vinpocetine
-
inhibitor of activated isoform PDE4
XAP2
-
noncompetitive inhibition, aryl-hydrocarbon receptor-interacting protein XAP2 inhibits PDE4A5 activity by XAP2 does not require any intermediate proteins. XAP2 inhibits PDE4A5 and not other PDE4 isoforms
-
zaprinast
-
10% inhibition at 0.05 mM
zaprinast
Q4ZHU6
-
zaprinast
O89084, Q9QXI7
0.1 mM, 67% inhibition; 0.1 mM, 72% inhibition
zaprinast
-
-
zaprinast
-
-
zardaverine
-
weak inhibitior
zardaverine
-
-
Zl-n-91
-
selective PDE4 inhibitor, Zl-n-91 at 0.03, 0.3 or 3 mg/kg dose dependently inhibits PDE4 activity
Zn2+
-
more than 90% inhibition at 0.05 mM Zn2+ in the presence of 0.1 mM EDTA, inhibition can be greatly relieved with EDTA at 0.30 mM
Zn2+
-
the 3',5'-phosphodiesterase enzyme activities of PdeA and PdeB are reduced to 24% and 28%, respectively, by 0.05 mM Zn2+ at pH 8.0 in 50 mM Tris-HCl buffer
MK298
-
-
additional information
-
IC 50 for sildenafil and tadalafil is above 10000 nM, PDE7; IC50 for sildenafil is above 100000 nM and IC50 for tadalafil and vardenafil is above 10000 nM, PDE8
-
additional information
Q309F4
not inhibitory: 3-isobutyl-1-methylxanthine, papaverine, theophylline; TcrPDEA1 is resistant to the typical phosphodiesterase inhibitors, such as IBMX, papaverine and theophylline
-
additional information
-
treatment with oxidant t-butylhydroperoxide results in release of significant amounts of interleukin-8, which is prevented by inhibition of enzyme isoforms PDE1 and PDE4
-
additional information
-
the oxidant t-butylhydroperoxide signifcantly increases the cytosolic calcium concentration. Inhibition of both isoforms PDE1 and PDE4 completely prevent the t-butylhydroperoxide stimulated TNF-alpha release
-
additional information
-
the enzyme is insensitive (up to 100 mM) to a variety of PDE inhibitors including rolipram, zaprinast, vinpocetine, SKF-94120, and IBMX
-
additional information
-
EHNA, milrinone, rolipram, and zaprinast, which are PDE2, PDE3, and PDE4 inhibitors, respectively, do not inhibit the PDE7B activity up to concentrations of 0.100 mM
-
additional information
Q9NP56
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
zaprinast, rolipram, and milrinone do not significantly inhibit PDE7B
-
additional information
-
removal of the last 35 amino acids of an N-terminal 80-residue highly conserved region (UCR2) results in a 6fold increase in PDE activity, providing evidence that this part of the molecule acts as an intramolecular inhibitor
-
additional information
-
no inhibition by siguazodan or zaprinast
-
additional information
-
not affected by Ca2+, Fe2+, Mn2+, HSCH2CH2OH, methanol, and dimethylsulfoxide
-
additional information
-
he 3',5'-phosphodiesterase activities of PdeA and PdeB are not inhibited by theophylline, 3-isobuthyl-1-methylxanthine, and beta-glycerophosphate
-
additional information
-
not inhibited by quercetin-3,7,3',4'-O-tetramethylether
-
additional information
-
not inibited by alpha-bisabolol, caffeic acid, ferulic acid, quinic acid, rutin, chlorogenic acid, herniarin, and umbelliferone
-
additional information
-
not inhibited by cilostamide
-
additional information
-
unlike other cAMP-specific PDEs, PDE8s are insensitive to a common nonselective PDE inhibitor, 3-isobutyl-1-methylxanthine (IBMX), but ca be inhibited by a high concentration of dipyridamole
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Calmodulin
-
required, Km value 0.000057 mM
cAMP
Q49UB9
binds to N-terminus and GAF domain, affinity of 0.0005 mM; binds to N-terminus and GAF domain, affinity of 0.001 mM
cGMP
Q49UB9
binds to N-terminus and GAF domain, affinity of 0.003 mM
EDTA
-
EDTA at 0.10 mM slightly activates PDE4
extract of Ginkgo biloba
-
some beneficial effects of extract of Ginkgo biloba might be due to its modulating influences on cellular cyclic AMP levels via activation of membrane-bound PDE
-
follicle-stimulating hormone
-
stimulation
-
haloperidol
-
chronic treatment with 20 mg/kg clozapine increases PDE4B2 and PDE4B4 expression by 102 and 71%, respectively
isoproterenol
-
0.001 mM isoproterenol triggers a sustained, 2fold increase in PDE4 activity
isoproterenol
-
PDE4 activity is stimulated with 0.01 mM isoproterenol
additional information
Q49UB9
enzyme does not bind cGMP
-
additional information
Q309F4
no effector: Ca2+, calmodulin
-
additional information
Q846Z1
expression of cpdA is activated by the cAMP-cAMP receptor protein complex via direct binding to the regulatory region
-
additional information
-
PDE4B1, PDE4B2, PDE4B3, and PDE4B4 are not changed by chronic haloperidol treatment
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00025
3',5'-cAMP
-
30C, pH 8.0, PDE7
0.0007
3',5'-cAMP
-
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.00099
3',5'-cAMP
Q6S996, Q6S997
-
0.0018
3',5'-cAMP
-
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.0025
3',5'-cAMP
-
30C, pH 8.0, PDE4
0.0032
3',5'-cAMP
-
-
0.0033
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.005
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.0067
3',5'-cAMP
D4P095
the addition of FeCl2 does not significantly influence substrate affinity of CdpA increases the rate of the 5'-AMP production, pH and temperature not specified in the publication
0.00698
3',5'-cAMP
Q6S996, Q6S997
-
0.0088
3',5'-cAMP
-
-
0.01
3',5'-cAMP
Q86H13
37C, pH 7.0
1.6
3',5'-cGMP
-
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.00003
adenosine 3',5'-cyclic phosphate
P70453
-
0.000055
adenosine 3',5'-cyclic phosphate
-
-
0.0001
adenosine 3',5'-cyclic phosphate
-
-
0.0001
adenosine 3',5'-cyclic phosphate
P70453
PDE7A2
0.00013
adenosine 3',5'-cyclic phosphate
-
PDE7B expressed in transfected COS-7 cells
0.00015
adenosine 3',5'-cyclic phosphate
O88502
-
0.0002
adenosine 3',5'-cyclic phosphate
Q9NP56
-
0.0002
adenosine 3',5'-cyclic phosphate
P70453
PDE7A1
0.002
adenosine 3',5'-cyclic phosphate
-
mutant enzyme L391A
0.0024
adenosine 3',5'-cyclic phosphate
Q9GQU6
-
0.003
adenosine 3',5'-cyclic phosphate
-
-
0.0032
adenosine 3',5'-cyclic phosphate
-
wild-type enzyme
0.0038
adenosine 3',5'-cyclic phosphate
-
-
0.0038
adenosine 3',5'-cyclic phosphate
-
mutant enzyme F484Y; mutant enzyme W375F; mutant enzyme W605F
0.0042
adenosine 3',5'-cyclic phosphate
-
mutant enzyme W375Y
0.0043
adenosine 3',5'-cyclic phosphate
-
-
0.0044
adenosine 3',5'-cyclic phosphate
-
mutant enzyme V501A
0.0054
adenosine 3',5'-cyclic phosphate
P14646
-
0.0058
adenosine 3',5'-cyclic phosphate
-
-
0.0069
adenosine 3',5'-cyclic phosphate
-
mutant enzyme D440A
0.007
adenosine 3',5'-cyclic phosphate
O89084, Q9QXI7
-
0.0073
adenosine 3',5'-cyclic phosphate
Q6XG56
-
0.0074
adenosine 3',5'-cyclic phosphate
-
mutant enzyme A590C
0.0092
adenosine 3',5'-cyclic phosphate
O89084, Q9QXI7
-
0.0096
adenosine 3',5'-cyclic phosphate
Q86H13
-
0.0112
adenosine 3',5'-cyclic phosphate
Q49UB9
pH 7.5, 30C
0.0164
adenosine 3',5'-cyclic phosphate
-
mutant enzyme D440N
0.02
adenosine 3',5'-cyclic phosphate
Q4ZHU6
-
0.0244
adenosine 3',5'-cyclic phosphate
-
mutant enzyme P595I
0.191
adenosine 3',5'-cyclic phosphate
Q309F4
-
0.277
adenosine 3',5'-cyclic phosphate
-
30C
0.0001
cAMP
-
-
0.0008
cAMP
P27815, Q08499
pH 7.5, 25C
0.0015
cAMP
P27815, Q08499
pH 7.5, 25C
0.0045
cAMP
P27815, Q08499
pH 7.5, 25C
0.0051
cAMP
P27815, Q08499
pH 7.5, 25C
0.0058
cAMP
Q07343
30C
0.0096
cAMP
-
pH 7.0, 22C
0.01
cAMP
Q86H13
pH 7.0, 37C
0.191
cAMP
Q309F4
pH 7.5, 30C
0.24
cGMP
P27815, Q08499
pH 7.5, 25C
0.427
cGMP
P27815, Q08499
pH 7.5, 25C
0.124
guanosine 3',5'-cyclic phosphate
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.00093
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
0.00096
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
4
3',5'-cAMP
-
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
4.3
3',5'-cAMP
-
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
1.6
3',5'-cGMP
-
wild type PDE8A1 catalytic domain, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.3
cAMP
-
-
0.66
cAMP
P27815, Q08499
pH 7.5, 25C
1.56
cAMP
P27815, Q08499
pH 7.5, 25C
5.4
cAMP
P27815, Q08499
pH 7.5, 25C
6.7
cAMP
P27815, Q08499
pH 7.5, 25C
0.48
cGMP
P27815, Q08499
pH 7.5, 25C
1.19
cGMP
P27815, Q08499
pH 7.5, 25C
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.19
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
969
0.29
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40C
969
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000085
(R)-rolipram
-
-
0.001
10-(3-pyrrolidin-1-ylpropyl)-2-(trifluoromethyl)-10H-phenoxazine
-
pH 7.5, 30C
0.0008
10-(4'-N-morpholinobutyl)-2-chlorophenoxazine
-
-
0.00101
10-(4'-N-morpholinobutyl)-2-trifluoromethylphenoxazine
-
-
0.0007
10-(4'-N-piperidinobutyl)-2-chlorophenoxazine
-
-
0.00054
10-(4'-N-piperidinobutyl)-2-trifluoromethylphenoxazine
-
-
0.00058
10-(4'-N-pyrrolidinobutyl)-2-chlorophenoxazine
-
-
0.00018
10-(4'-N-pyrrolidinobutyl)-2-trifluoromethylphenoxazine
-
-
0.00097
10-[3'-[(beta-hydroxyethyl)-piperazino]propyl]-2-trifluoromethylphenoxazine
-
-
0.00087
10-[30-[(beta-hydroxy ethyl)-piperazino]propyl]-2-chlorophenoxazine
-
-
0.00105
10-[4'-(N-diethylamino)-butyl]-2-chlorophenoxazine
-
-
0.0006
10-[4'-(N-diethylamino)butyl]-2-trifluoromethylphenoxazine
-
-
0.00038
10-[4'-[(beta-hydroxy ethyl)-piperazino]butyl]-2-trifluoro-methylphenoxazine
-
-
0.00055
10-[4'-[(beta-hydroxy-ethyl)piperazino]butyl]-2-chlorophenoxazine
-
-
0.000002
4-(3,4-dimethoxyphenyl)-2-{5-[(2-{5-[2-(2-fluoro-5-methoxyphenyl)ethyl]tetrahydrofuran-2-yl}ethyl)amino]pentyl}-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
isoform PDE4D3, pH and temperature not specified in the publication
0.0018
4-[(3-butoxy-4-methoxyphenyl)methyl]-2-imidazolidinone
-
-
0.000068
apremilast
-
PDE4 purified from U-937 cells, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.000097
cilomilast
-
-
0.000114
cilomilast
Q07343
30C
0.0183
diazepam
O89084, Q9QXI7
-
0.0493
diazepam
O89084, Q9QXI7
-
0.00025
R-rolipram
-
-
0.00038
R-rolipram
-
-
0.0076
RO 201724
-
-
0.000037
rolipram
-
particulate enzyme
0.000324
rolipram
-
-
0.00038
rolipram
Q07343
30C
0.0016
rolipram
-
cytosolic enzyme
0.002
rolipram
-
-
0.074
rolipram
-
-
0.000099
XAP2
-
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.1195
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.1195 mM, PDE7
0.31
(2R,3R)-3-(6-amino-9H-purin-9-yl)nonan-2-ol
-
IC50: 0.31 mM, PDE4
0.00043
(2Z)-9,10-dimethoxy-3-methyl-2-[(2,4,6-trimethylphenyl)imino]-2,3,6,7-tetrahydro-4H-pyrimido[6,1-a]isoquinolin-4-one
-
IC50: 0.00043 mM, PDE4
0.000085
(4aS,8aR)-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0001
1-(2,4-dichlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0011
1-(2-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0009
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0012
1-(3-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0024
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0034
1-(3-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0002
1-(4-chlorobenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0006
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0009
1-(4-methylbenzyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.002
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0012
1-benzyl-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
-
-
0.0023
10-(4'-N-pyrrolidinobutyl)-2-trifluoromethylphenoxazine
-
-
0.0031
10-[4'-[(b-hydroxy ethyl)-piperazino]butyl]-2-trifluoro-methylphenoxazine
-
-
0.0044
10-[4'-[(b-hydroxy-ethyl)piperazino]butyl]-2-chlorophenoxazine
-
-
0.0203
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0203 mM, PDE7
0.0453
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.0453 mM, PDE4
0.00381
3-isobutyl-1-methyl-xanthine
-
pH 7.4, 30C
0.0322
3-isobutyl-1-methyl-xanthine
-
wild-type enzyme
0.175
3-isobutyl-1-methyl-xanthine
-
mutant enzyme D440N
2
3-isobutyl-1-methyl-xanthine
-
soluble enzyme
3
3-isobutyl-1-methyl-xanthine
-
particulate enzyme
0.0021
3-isobutyl-1-methylxanthine
P70453
-
0.0045
3-isobutyl-1-methylxanthine
P70453
-
0.007
3-isobutyl-1-methylxanthine
-
IC50: 0.007 mM, PDE7
0.00737
3-isobutyl-1-methylxanthine
Q9NP56
pH 7.4, 30C
0.0099
3-isobutyl-1-methylxanthine
-
-
0.0658
3-isobutyl-1-methylxanthine
-
mutant enzyme T748A, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.1262
3-isobutyl-1-methylxanthine
Q4ZHU6
-
0.304
3-isobutyl-1-methylxanthine
Q9GQU6
-
0.698
3-isobutyl-1-methylxanthine
-
wild type enzyme, in 20 mM Tris-HCl, pH 7.5, 4 mM MnCl2, at 24C
0.0059
3-isobuytl-1-methylxanthine
-
-
0.0087
4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone
-
PDE4
0.00018
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Q13946
pH not specified in the publication, 30C
0.0066
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Q13946
pH not specified in the publication, 30C
0.0073
4-[(2-chloro-4-nitrophenyl)thio]-pyridine
Q13946
pH not specified in the publication, 30C
0.00057
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
P27815, Q08499
pH 7.5, 25C
0.00065
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
P27815, Q08499
pH 7.5, 25C
0.0033
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
P27815, Q08499
pH 7.5, 25C
0.0057
4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid
P27815, Q08499
pH 7.5, 25C
0.0513
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0513 mM, PDE7
0.1008
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.1008 mM, PDE4
0.0041
apigenin
-
-
0.0102
apigenin-7-O-glucoside
-
-
0.00002
apremilast
-
recombinant isoform PDE4A4, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.00003
apremilast
-
recombinant isoform PDE4D3, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.000049
apremilast
-
recombinant isoform PDE4B2, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.00005
apremilast
-
recombinant isoform PDE4C2, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.000074
apremilast
-
PDE4 purified from U-937 cells, using 0.001 mM cAMP as substrate, pH and temperature not specified in the publication
0.0004
AWD 12-250
-
mutant enzyme D440N
0.0097
AWD 12-250
-
wild-type enzyme
0.000015
AWD12-281
-
wild-type enzyme
0.0205
AWD12-281
-
mutant enzyme D440N
0.0085
Biochanin A
-
IC50: 0.0085 mM, more selectively inhibits PDE4 than PDE1 or PDE2
0.0002
BRL-50481
-
pH and temperature not specified in the publication
19
Caffeine
-
particulate enzyme
2.401
cAMP-N1-oxide
-
wild-type enzyme
2.91
cAMP-N1-oxide
-
mutant enzyme D440N
0.0005
CI-1044
-
pH and temperature not specified in the publication
0.008
Cibacron blue
-
soluble enzyme
0.02
Cibacron blue
-
particulate enzyme
0.000101
cilomilast
P27815
-
0.000114
cilomilast
-
-
0.022
Cilostamide
-
IC50: 0.022 mM, PDE7
0.0888
Cilostamide
-
IC50: 0.0888 mM, PDE4
0.099
Cilostamide
-
IC50: 0.099 mM, PDE4
0.0214
cilostazol
-
IC50: 0.0214 mM, PDE7
0.088
cilostazol
-
IC50: 0.088 mM, PDE4
0.0000003
cis-(+)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000088
cis-(-)-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000004
cis-2-[(E)-4-(1H-imidazol-1-yl)but-2-enyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000052
cis-2-[2-[2-(1H-imidazol-1-yl)ethoxy]ethyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000013
cis-2-[4-(1,4-dioxa-8-azaspiro[4.5]decan-8-ylmethyl)-benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000007
cis-2-[4-[(1H-imidazol-1-yl)methyl]benzyl]-4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000013
cis-4-(3,4-dimethoxyphenyl)-2-[2-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000014
cis-4-(3,4-dimethoxyphenyl)-2-[3-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.000001
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000009
cis-4-(3,4-dimethoxyphenyl)-2-[4-(morpholinomethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000082
cis-4-(3,4-dimethoxyphenyl)-2-[4-(piperidin-1-ylmethyl)benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.000002
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-methylpiperazin-1-yl)methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000009
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(4-oxopiperidin-1-yl)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000097
cis-4-(3,4-dimethoxyphenyl)-2-[4-[(dimethylamino)-methyl]benzyl]-4a,5,8,8a-tetrahydrophthalazin-1(2H)-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000459
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.1.0]hept-4-en-2-one
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.0000164
cis-5-(3,4-dimethoxyphenyl)-3-[4-(morpholinomethyl)benzyl]-3,4-diazabicyclo[4.2.0]oct-4-en-2-one hydrochloride
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.00008
D-22888
-
wild-type enzyme
0.0048
D-22888
-
mutant enzyme D440N
0.0005
denbufylline
-
-
0.0094
diazepam
O89084, Q9QXI7
-
0.043
diazepam
O89084, Q9QXI7
-
0.0168
dioclein
-
isoform PDE4, pH and temperature not specified in the publication
0.0202
diosmetin
-
IC50: 0.0202 mM, PDE4
0.000146
dipyridamole
Q4ZHU6
-
0.00051
dipyridamole
-
pH 7.4, 30C
0.0011
dipyridamole
-
-
0.00113
dipyridamole
Q49UB9
pH 7.5, 30C
0.00194
dipyridamole
Q9NP56
pH 7.4, 30C
0.0045
dipyridamole
O88502
-
0.009
dipyridamole
P70453
-
0.0113
dipyridamole
Q49UB9
30C, pH 7.5
0.013
dipyridamole
-
IC50: 0.013 mM
0.015
dipyridamole
Q49UB9
30C, pH 7.5
0.017
dipyridamole
Q6XG56
-
0.027
dipyridamole
Q9GQU6
-
0.042
dipyridamole
P70453
-
0.009
dipyridimole
-
-
0.015
E4021
-
-
0.128
EHNA
Q49UB9
30C, pH 7.5
0.217
erythro-9-(2-hydroxy-3-nonyl)-adenine hydrochloride
Q6XG56
-
0.13
erythro-9-[3-(2-hydroxynonyl)]-adenine
P70453
-
0.0013
etazolate
Q4ZHU6
-
0.025
etazolate
-
IC50: 0.025 mM
0.127
etazolate
Q9GQU6
-
1.3
etazolate
Q4ZHU6
IC50: 1.3 mM
0.008
ethaverine
-
IC50: 0.008 mM
0.000082
ethyl 2-([4-(3-carbamoylpiperazin-1-yl)-6-[4-(dimethylamino)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000031
ethyl 2-([4-[(3,4-dimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000076
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000083
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00013
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-(morpholin-4-yl)pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00012
ethyl 2-([4-[4-(dimethylamino)piperidin-1-yl]-6-[3-(hydroxymethyl)piperidin-1-yl]pyrimidin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 2-([7-ethyl-6-[(4-sulfamoylbenzyl)amino]-7H-purin-2-yl]amino)-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000063
ethyl 2-[[4,6-bis(4-hydroxypiperidin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000056
ethyl 2-[[4-[4-[2-(dimethylamino)ethyl]piperazin-1-yl]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl]amino]-4-methyl-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00027
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00027 mM, PDE4D
0.00031
ethyl 3,5-dimethyl-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00031 mM, PDE4B
0.017
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
-
IC50: 0.017 mM, PDE4B
0.019
ethyl 3,5-dimethyl-1-quinolin-8-yl-1H-pyrazole-4-carboxylate
-
IC50: 0.019 mM, PDE4D
0.015
ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate
-
IC50: 0.015 mM, PDE4B
0.019
ethyl 3,5-dimethyl-1H-pyrazole-4-carboxylate
-
IC50: 0.019 mM, PDE4D
0.00088
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.00088 mM, PDE4D
0.0015
ethyl 3-(4-chlorophenyl)-1-phenyl-1H-pyrazole-4-carboxylate
-
IC50: 0.0015 mM, PDE4B
0.06
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
-
IC50: 0.06 mM, PDE4B
0.082
ethyl 3-methyl-5-(4-methylphenyl)-1H-pyrazole-4-carboxylate
-
IC50: 0.082 mM, PDE4D
0.000039
ethyl 4-methyl-2-([4-(4-methylpiperazin-1-yl)-6-[methyl(3,4,5-trimethoxybenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.0001
ethyl 4-methyl-2-([4-(methylamino)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 4-methyl-2-([4-(piperazin-1-yl)-6-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00022
ethyl 4-methyl-2-([4-[(4-sulfamoylbenzyl)amino]pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.00001
ethyl 4-methyl-2-([4-[methyl(3,4,5-trimethoxybenzyl)amino]-6-(piperazin-1-yl)pyrimidin-2-yl]amino)-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.000006
ethyl 4-methyl-2-[[4-(piperazin-1-yl)-7-(3,4,5-trimethoxybenzyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-2-yl]amino]-1,3-thiazole-5-carboxylate
-
temperature not specified in the publication, in 20 mM Tris-HCl, pH 7.4
0.025
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
-
IC50: 0.025 mM, PDE4B
0.05
ethyl 5-amino-1-(4a,5,6,7,8,9a-hexahydro[1]benzothieno[2,3-d]pyrimidin-4-yl)-1H-pyrazole-4-carboxylate
-
IC50: 0.05 mM, PDE4D
0.0095
genistein
-
IC50: 0.0095 mM, PDE4
0.0282
hesperetin
-
IC50: 0.0282 mM, PDE4
0.0118
hyperoside
-
-
0.000085
IR-202
-
pH and temperature not specified in the publication
0.0000004
L-826,141
-
isozymes PDE4B and PDE4D
0.0000013
L-826,141
-
isozymes PDE4C and PDE4A
0.00421
LAS-31025
-
wild-type enzyme
0.00728
LAS-31025
-
mutant enzyme D440N
0.0013
luteolin
-
-
0.0191
luteolin
-
IC50: 0.0191 mM, PDE4
0.043
luteolin-7-glucoside
-
IC50: 0.043 mM, PDB4, dual inhibitionof PDE2 and PDE4
0.0149
luteolin-7-O-glucoside
-
-
0.04
methylisobutylxanthine
-
-
0.0033
Milrinone
-
mutant enzyme D440N
0.00635
Milrinone
-
wild-type enzyme
0.0175
Milrinone
-
IC50: 0.0175 mM, PDE4
0.0389
myricetin
-
IC50: 0.0389 mM, PDE4
0.0021
N-[2-(5-chloro-2-nitrophenylthio)phenyl]acetamide
Q13946
pH not specified in the publication, 30C
0.0000143
N-[3-(1H-imidazol-1-yl)propyl]-2-[cis-4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,8,8a-tetrahydrophthalazin-2(1H)-yl]acetamide
-
in Tris-HCl (pH 7.6), 100 mM NaCl, 150 mM MgCl2, and 0.5% (w/v) polyethylene glycol 6000, at 30C
0.561
N6-monobutyyl-cAMP
-
wild-type enzyme
1.13
N6-monobutyyl-cAMP
-
mutant enzyme D440N
0.3
OPC-3911
-
soluble enzyme
0.8
OPC-3911
-
particulate enzyme
0.0125
papaverine
P70453
-
0.01288
papaverine
Q4ZHU6
-
0.022
papaverine
P70453
-
0.03
papaverine
-
IC50: 0.03 mM
0.111
papaverine
Q6XG56
-
0.127
papaverine
Q9GQU6
-
0.174
papaverine
O88502
-
0.0149
patuletin-7-O-glucoside
-
-
0.0000002
PF-04957325
-
PDE8B, pH and temperature not specified in the publication
0.0000007
PF-04957325
-
PDE8A, pH and temperature not specified in the publication
0.0114
prunetin
-
IC50: 0.0114 mM, PDE4
0.0099
quercetin
-
IC50: 0.0099 mM, PDE4
0.0099
quercetin
-
PDE4
0.0185
quercetin-3,5,7,3',4'-O-pentaacetate
-
PDE4
0.0051
quercetin-3,5,7,3',4'-O-pentamethylether
-
PDE4
0.0158
quercetin-3,7,4'-O-trimethylether
-
PDE4
0.0039
quercetin-3-O-methyl-5,7,3',4'-O-tetraacetate
-
PDE4
0.0285
quercetin-3-O-methylether
-
PDE4
0.34
quinazolinamine
-
IC50: 0.34 mM, PDE4
0.000042
Ro20-1724
-
-
0.002
Ro20-1724
-
-
0.0022
Ro20-1724
-
-
0.0000001
roflumilast
-
isozymes PDE4A, PDE4B, and PDE4D
0.0000006
roflumilast
-
isozyme PDE4C
0.00001
rolipram
-
in 20 mM Tris-HCl at pH 7.4, 10 mM MgCl2, and 0.1 mM EDTA, at 30C
0.000011
rolipram
P27815
-
0.000021
rolipram
-
-
0.00005
rolipram
-
-
0.000083
rolipram
P14646
-
0.0001
rolipram
-
-
0.000143
rolipram
P14270, P14646
-
0.000148
rolipram
-
-
0.000149
rolipram
-
mutant enzyme A590C
0.00017
rolipram
O89084, Q9QXI7
-
0.000181
rolipram
-
wild-type enzyme
0.0002
rolipram
-
mutant enzyme L391A
0.000202
rolipram
-
mutant enzyme W375Y
0.000256
rolipram
-
mutant enzyme V501A
0.000293
rolipram
-
mutant enzyme W605F
0.00032
rolipram
-
mutant enzyme F484Y
0.00038
rolipram
-
-
0.0004
rolipram
-
-
0.00045
rolipram
-
IC50: 0.00045 mM, PDE4
0.0007
rolipram
-
isoform PDE4, pH and temperature not specified in the publication
0.001
rolipram
-
-
0.0011
rolipram
O89084, Q9QXI7
-
0.0023
rolipram
-
PDE4
0.00245
rolipram
-
mutant enzyme P595I
0.01046
rolipram
Q4ZHU6
-
0.04265
rolipram
-
mutant enzyme D440A
0.08923
rolipram
-
mutant enzyme D440N
0.18
rolipram
-
mutant enzyme W375F
0.18
rolipram
P70453
-
0.28
rolipram
-
IC50: 0.28 mM
0.6
rolipram
-
particulate enzyme
0.7
rolipram
-
soluble enzyme
10.46
rolipram
Q4ZHU6
IC50: 10.46 mM
0.0000016
RP-73401
-
IC50: 0.0000016 mM, PDE4
0.000001
RPR-73401
-
wild-type enzyme
0.0178
RPR-73401
-
mutant enzyme D440N
0.000113
SB 207499
-
-
0.000117
SB 207499
P14270, P14646
-
0.000105
SCH 351591
-
-
0.000109
SCH 351591
P14270, P14646
-
0.0015
SCH51866
-
PDE7B expressed in transfected COS-7 cells
0.035
SCH51866
P70453
-
0.044
SCH51866
P70453
-
0.001
sildenafil
-
IC50: 0.001 mM
0.00319
sildenafil
-
IC50: 3190 nM, PDE4
0.0395
sildenafil
-
wild-type enzyme
0.0861
sildenafil
-
mutant enzyme D440N
0.01
tadalafil
-
IC50: above 10000 nM, PDE4
3
theophylline
-
particulate enzyme
30
theophylline
-
soluble enzyme
0.0025
trequinsin
-
IC50: 0.0025 mM
1.958
trequinsin
Q4ZHU6
-
0.002055
vardenafil
-
IC50: 2055 nM, PDE4
0.0046
vardenafil
-
IC50: 4600 nM, PDE4
0.059
vinpocetine
-
-
0.131
vinpocetine
-
isoform PDE4, pH and temperature not specified in the publication
0.134
vinpocetine
Q6XG56
-
0.04
zaprinast
-
particulate enzyme
0.0525
zaprinast
-
mutant enzyme D440N
0.728
zaprinast
Q4ZHU6
-
2.8
zaprinast
-
soluble enzyme
0.0583
Milrinone
-
IC50: 0.0583 mM, PDE7
0.01
additional information
-
IC 50 for sildenafil and tadalafil is above 10000 nM, PDE7
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.5 - 8.5
-
PdeA and PdeB have slightly alkaline pH optima (pH 7.5-8.5) for 3',5'-cAMP hydrolysis in 0.1 M Tris-HCl buffer
7.6
D4P095
assay at
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.3 - 9.2
-
pH 6.3: about 40% of maximal activity, pH 9.2: about 80% of maximal activity
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
25
D4P095
assay at
40
-
the optimum temperatures for the 3',5'-cAMP phosphodiesterase activity of PdeA is 40C
50
-
the optimum temperatures for the 3',5'-cAMP phosphodiesterase activity of PdeB is 50C
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6.7
-
isoelectric focusing
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
lung epithelial cell
Manually annotated by BRENDA team
-
PDE4A expression in GH-secreting adenomas is highly variable and independent from the presence of the gsp oncogene, PDE4B expression in GH-secreting adenomas is highly variable and independent from the presence of the gsp oncogene, the level of PDE4C transcripts in gsp+ tumors is significantly higher than that found in gsp- adenomas, the level of PDE4D transcripts in gsp+ tumors is significantly higher than that found in gsp- adenomas
Manually annotated by BRENDA team
-
of newborn mice
Manually annotated by BRENDA team
O95263
tumor tissues from patients with isolated micronodular adrenocortical disease and no mutations in the coding PDE8B sequence or any other related genes (PRKAR1A, PDE11A) show downregulated PDE8B expression compared to normal adrenal cortex. PDE8B is a PDE gene linked to isolated micronodular adrenocortical disease. It is a candidate causative gene for other adrenocortical lesions linked to the cAMP signaling pathway and possibly for tumors in other tissues
Manually annotated by BRENDA team
-
PDE4, PDE7, PDE8
Manually annotated by BRENDA team
-
PDE7A1 co-localizes with PKA II in the Golgi centrosome region
Manually annotated by BRENDA team
P14270, P14646
high activity
Manually annotated by BRENDA team
P27815
and skeletal muscle, predominant expression
Manually annotated by BRENDA team
Q07343
isoform PDE4B5 is brain-specific
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
-
of normal and triethyltin-intoxicated rats
Manually annotated by BRENDA team
-
PDE4B5 is brain-specific
Manually annotated by BRENDA team
P70453
PDE7A1
Manually annotated by BRENDA team
B1PSD9
in the brain, PDE4D11 expression levels increase in the cerebellum, but decrease in the hippocampus with progressive age
Manually annotated by BRENDA team
-
parietal, frontal, temporal cortex, hippocampus, striatum, thalamus, hypothalamus, substantia nigra, nucleus accumbens, cerebellum
Manually annotated by BRENDA team
-
isoforms PDE4A, PDE4D, PDE7A, PDE8A, PDE8B show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE7A, PDE7B does not change with age. Age-related increases in PDE11A4, PDE8A3, PDE8A4/5, and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents, as are age-related increases in PDE8A3 protein expression in the striatum
Manually annotated by BRENDA team
-
carcinoma of salivary gland
Manually annotated by BRENDA team
-
phosphodiesterase 4 is detected in smooth muscle cells of the wall, and in the cytoplasm of luminal endothelial cells of cavernous arteries
Manually annotated by BRENDA team
B1PSD9
PDE4D11 expression levels increase in the cerebellum with progressive age
Manually annotated by BRENDA team
-
PDE4 is observed in the nonvascular smooth musculature of the corpus cavernosum clitoris, sinusoidal endothelial and subendothelial layers, and nerve fibers innervating the tissue, presence of isoform PDE4 in nonvascular smooth musculature of the corpus carnosum, in sinusoidal endothelial and subendothelial layers, and nerve fiber innervating the tissue
Manually annotated by BRENDA team
-
presence of isoform PDE4 in nonvascular smooth musculature of the corpus carnosum
Manually annotated by BRENDA team
-
age-related increases in isoform PDE8A3 protein expression are confirmed in hippocampus of old versus young rodents
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
-
sinusoidal endothelial and subendothelialn layer of clitoris, presence of isoform PDE4
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
-
lowering cyclic adenosine-3',5'-monophosphate levels by expression of a cAMP-specific phosphodiesterase decreases intrinsic pulsatile gonadotropin-releasing hormone secretion from GT1 cells
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
P70453
PDE7A2
Manually annotated by BRENDA team
B1PSD9
lowest expression in heart
Manually annotated by BRENDA team
-
neonatal cardiac myocyte
Manually annotated by BRENDA team
B1PSD9
PDE4D11 expression levels decrease in the hippocampus with progressive age
Manually annotated by BRENDA team
-
age-related increases in isoforms PDE8A3, PDE8A4/5 and PDE1C1 protein expression are confirmed in hippocampus of old versus young rodents
Manually annotated by BRENDA team
-
age-related increases in isoforms PDE8A3, PDE8A4/5 protein expression are confirmed in hippocampus of old versus young rodents. Relative to young rats, the hippocampi of old rats demonstrate strikingly decreased phosphorylation of GluR1, CaMKIIalpha, and CaMKIIbeta, decreased expression of the transmembrane AMPA regulatory proteins gamma2 (a.k.a. stargazin) and gamma8, and increased trimethylation of H3K27. Expression of isoforms of PDE8A4/5, PDE8A3 correlate with these functional endpoints in young but not old rats
Manually annotated by BRENDA team
-
human middle ear epithelial cell
Manually annotated by BRENDA team
-
macrophage cell
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
P70453
PDE7A1
Manually annotated by BRENDA team
-
the phosphodiesterase 4B4 isoform present in kidney tissue from spontaneously hypertensive rats, hypertensive Dahl salt-sensitive rats, and Dahl salt-resistant rats, phosphodiesterase 4B expression is detected in the renal vasculature, proximal tubules, and distal tubules
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
B1PSD9
highest expression level
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
P70453
PDE7A1
Manually annotated by BRENDA team
-
PDE4B. Ablation of PDE4B partially protects mice from LPS-induced shock
Manually annotated by BRENDA team
-
gingiva-derived malignant melanoma cell, expression of variants PDE4B and PDE4D
Manually annotated by BRENDA team
-
strong expression of isoform PDE4 throughout the nervous system
Manually annotated by BRENDA team
-
human bronchial epithelial cell
Manually annotated by BRENDA team
-
cultured, PDE7
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
P70453
most highly expressed in pancreas followed by brain, heart, thyroid, skeletal muscle, eye, ovary, submaxillary gland, epididymus, and liver, PDE7A1
Manually annotated by BRENDA team
P70453
PDE7A1
Manually annotated by BRENDA team
-
abundantly present in the fibromusclular stroma as well as in glandular structures of the transition zone
Manually annotated by BRENDA team
P14270, P14646
high activity
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
-
carcinoma of salivary gland
Manually annotated by BRENDA team
-
immature cell. Almost all PDE4D variants are expressed throughout the early postpartum period with a specific increase in PDE4 activity in both soluble and particulate fraction of 20 day old Sertoli cells, isolated from 10-, 20-, and 30-days-old rats. Specific increase in PDE4 activity in both the soluble and particulate subcellular fractions of 20-days-old Sertoli cells. Almost all the PDE4D isoforms, known as the main cAMP-regulated rolipramsensitive PDE in Sertoli cells, are expressed throughout the early postpartum period, whereas only the short PDE4D isoforms (PDE4D1 and PDE4D2) are transcriptionally regulated by FSH. The subcellular distribution and expression of PDE4D proteins are unaffected by the developmental status of the Sertoli cells. Only the expression of short PDE4D1 appears to be upregulated by FSH and only in 20-days-old Sertoli cells, which suggests phenotype-dependent differential regulation of Pde4d1 mRNA translation
Manually annotated by BRENDA team
P27815
and brain, predominant expression
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order
Manually annotated by BRENDA team
-
of central cavernous arteries
Manually annotated by BRENDA team
B1PSD9
highest expression level
Manually annotated by BRENDA team
-
PDE4 is present in young and adult gland. During development PDE4 is the major PDE
Manually annotated by BRENDA team
P14270, P14646
high activity
Manually annotated by BRENDA team
-
weak activity
Manually annotated by BRENDA team
O88502
highest expression in testis, followed by eye, liver, skeletal muscle, heart, 7-day embryo, kidney, ovary, and brain in decreasing order. In testis PDE8 is expressed in the seminiferous epithelium in a stage-specific manner
Manually annotated by BRENDA team
-
numerous PDE4D gene-derived variants including PDE4D3, PDE4D5, PDE4D7, PDE4D8, and PDE4D9
Manually annotated by BRENDA team
-
monocytic cells may express different PDE4 isozymes, depending on their state of activation or differentiation. These isozymes could thus regulate intracellular cAMP levels at various stages of monocyte activation and could thereby be important in limiting the inflammatory response
Manually annotated by BRENDA team
additional information
-
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
Manually annotated by BRENDA team
additional information
-
mRNA expression levels of PDEs 4A, 4B, 4C and 4D are significantly higher in rats than in humans. Higher PDE4 expression levels are correlated with a higher enzyme activity level in rat leukocytes
Manually annotated by BRENDA team
additional information
-
PDE IVB is not detected in Placenta, liver, kidney, or pancreas
Manually annotated by BRENDA team
additional information
-
determination of tissue distribution and level of the different PDE isozymes via quantitative real-time PCR expresssion analysis, overview
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
colocalization of isoform PDE7A1 with protein kinase II in the golgi-centrosome region
Manually annotated by BRENDA team
Q38F42, Q38F46, Q8WQX9
-
Manually annotated by BRENDA team
-
of luminal endothelial cells of cavernous arteries
Manually annotated by BRENDA team
Q38F42, Q38F46, Q8WQX9
TbrPDEB2 is distributed between flagellum and cytoplasm
Manually annotated by BRENDA team
P27815
predominant localization, recombinant protein expressed in COS-7 cell
Manually annotated by BRENDA team
Q07343
uneven and predominant localization
Manually annotated by BRENDA team
-
PDE4B5 is distributed predominantly and unevenly within the cytosol
Manually annotated by BRENDA team
-
the enzyme associated with both the soluble and particulate fractions
Manually annotated by BRENDA team
P27815
when expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme is associated with membrane fractions
Manually annotated by BRENDA team
D0ERY7, D0ERY8
a fully functional GFP-tagged PdeH is cytosolic but associates dynamically with the plasma membrane and vesicular compartments
Manually annotated by BRENDA team
-
with the exception of one isoform PDE4A, PDE4 enzymes are primarily cytosolic enzymes
Manually annotated by BRENDA team
-
the enzyme is secreted by the plasmodium during migration
-
Manually annotated by BRENDA team
Q38F42, Q38F46, Q8WQX9
TbrPDEB2 is distributed between flagellum and cytoplasm
-
Manually annotated by BRENDA team
-
colocalization of isoform PDE7A1 with protein kinase II in the golgi-centrosome region
Manually annotated by BRENDA team
-
PDE4A splice variant RD1 contains a membrane-association signal which allows the targeted expression of RD1 within the Golgi complex of human follicular thyroid carcinoma cell lines FTC133 and FTC236
Manually annotated by BRENDA team
Q86H13
membrane-bound enzyme with an extracellular domain
Manually annotated by BRENDA team
P27815
about 20% of protein is associated with membrane, recombinant protein expressed in COS-7 cell
Manually annotated by BRENDA team
Q86H13
DdPDE4 is a unique membrane-bound phosphodiesterase with an extracellular catalytic domain regulating intercellular cAMP during multicellular development
Manually annotated by BRENDA team
-
helix-1 is important for intracellular targeting of PDE4A1 in living cells, facilitating membrane association, targeting to the trans-Golgi stack and conferring Ca2+-stimulated intracellular redistribution in a manner that is dependent on the phospholipase-D-mediated generation of phosphatidic acid
Manually annotated by BRENDA team
P27815
when expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme is associated with membrane fractions
Manually annotated by BRENDA team
-
isozyme PDE4A
Manually annotated by BRENDA team
-
PDE4 (56%) and PDE3 (44%) are the main cyclic phosphodiesterase activities in cardiac nuclei
Manually annotated by BRENDA team
Q07343
small part of enzyme is associated with the plasma membrane
Manually annotated by BRENDA team
-
long variants of PDE4D are mainly soluble
-
Manually annotated by BRENDA team
-
short variant PDE4D1 is mainly particulate
-
Manually annotated by BRENDA team
additional information
-
the soluble PDE4 activities are mainly related to the long PDE4D isoforms and short PDE4D1 is predominantly particulate
-
Manually annotated by BRENDA team
additional information
D0ERY7, D0ERY8
the deletion mutant the GFP-PdeL localizes predominantly to the nucleus
-
Manually annotated by BRENDA team
PDB
SCOP
CATH
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
-
PdeA, calculated from amino acid sequence; PdeA, SDS-PAGE
692369
31000
-
PdeB, calculated from amino acid sequence
692369
34000
-
PdeB, SDS-PAGE
692369
56000
-
gel filtration, sucrose density gradient centrifugation
135278
58000
-
-
681580
58000
-
PDE4B4 recombinant protein, SDS-PAGE
694373
62000
-
unphosphorylated PDE4B4
692587
66000
-
phosphorylated PDE4B4
692587
69000
-
PDE4B2 recombinant protein, SDS-PAGE
694373
79030
B1PSD9
calculated from amino acid sequence
691716
87000
-
PDE4B1 or PDE4B3 recombinant protein, SDS-PAGE, the 87000 Da band is termed PDE4B1/B3 due to difficulty of resolving it into separate bands using SDS-PAGE
694373
200000
-
gel filtration
688885
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
?
-
x * 61000, SDS-PAGE
?
O89084, Q9QXI7
x * 83000, SDS-PAGE
?
O89084, Q9QXI7
x * 93000, SDS-PAGE
?
-
x * 39000, SDS-PAGE, x * 38800, deduced from gene sequence, both N-terminally truncated enzyme
?
Q49UB9
x * 102500, calculated
?
P27815
x * 125000, SDS-PAGE, recombinant protein
?
Q07343
x * 58000, SDS-PAGE of isoform PDE4B5
?
P70453
x * 50000, PDE7A2, calculated from sequence, x * 50100, calculated from sequence, x * 57000, PDE7A1, calculated from sequence
monomer
D4P095
1 * 31000 Da, SDS-PAGE
additional information
-
enzyme contains two GAF domains and a catalytic domain highly homologous with that of the Trypanosoma brucei family
additional information
Q07343
isoform PDE4B5 is able to bind the scaffold protein DISC1
additional information
-
isoform PDE4D interacts with beta-arrestin. Identification of a binding site in the beta-arrestin 2 N-domain for the common PDE4D catalytic unit and two regions in the beta-arrestin 2 C domain that confer specificity for PDE4D5 binding. Reduced interaction of PDE4D5 with beta-arrestin mutants R26A, K18A, or T20A. R286, D291, and L215-H220 of beta-arrestin are important for binding PDE4D5, but not for PDE4D3. Interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation
additional information
-
isoform PDE7A1 associates with the dissociated C subunit of cAMP dependent protein kinase, but does not bind tetrameric protein kinase holoenzyme. Binding of protein kinase C subunit inhibits kinase activity in vitro, the N-terminal repeat region f PDE7A1 is sufficient for inhibition
additional information
-
signalling scaffold protein RACK, i.e. receptors for activated C-kinase, and beta-arrestin interact with enzyme in mutually exclusive manner at overlapping sites within the N-terminal region of PDE4D5 and at distinct sites within the catalytic domain. Alterations within the level of RACK1 expression may act to modulate signal transduction mediated by beta2-adrenergic receptor through increase in PDE4D5 recruited to the receptor
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
Q86H13
protein sequence predicts a leader sequence, two transmembrane segments, and an extracellular catalytic domain
phosphoprotein
P27815
phosphorylation of enzyme by cAMP-dependent protein kinase at S123, phosphorylation by cAMP-dependent protein kinase
phosphoprotein
-
phosphorylation of PDE-4D3 by protein kinase A produces a monophasic Mg2+ response curve. Phosphorylation of PDE-4D3 increased the sensitivity of the enzyme to inhibition by RS-25344 (about 100fold) and RS-33793 (about 330fold). Phosphorylation of PDE-4D3 induces an apparent conformation change that increases maximum velocity and sensitivity to inhibition by some analogues of nitraquazone
phosphoprotein
-
PDE4 activation is regulated via phosphorylation by PKA in the UCR or phosphorylation by ERK in the C-terminus, depending on the individual isoform
phosphoprotein
-
aryl-hydrocarbon receptor-interacting protein XAP2 attenuates the ability of cAMP-dependent protein kinase to phosphorylate PDE4A5
phosphoprotein
P14646
treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which is associated with the phosphorylation of PDE4B4 on Ser-56 within UCR1
phosphoprotein
-
protein kinase A catalyzes phosphorylation (at Ser-54) and activation of isoform PDE4D3. Protein phosphatase 2A associated with muscle A kinase-anchoring protein complexes promotes PDE4D3 dephosphorylation at Ser-54
phosphoprotein
-
phosphorylation of cAMP-specific PDE4A5 by MAPK-activated protein kinase 2, also called MAPKAPK2. PDE4A5 is phosphorylated at Ser147, within the regulatory UCR1, ultraconserved region 1, domain conserved among PDE4 long isoforms. Phosphorylation by MK2, although not altering PDE4A5 activity, markedly attenuates PDE4A5 activation through phosphorylation by protein kinase A. Phosphorylation by MK2 also triggers a conformational change in PDE4A5 that attenuates PDE4A5 interaction with proteins whose binding involves UCR2, such as DISC1 and AIP, but not the UCR2-independent interacting scaffold protein beta-arrestin
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
catalytic domain of inactive mutant D201N in complex with substrate cAMP at 1.56 A resolution. Q369 forms only one hydrogen bond ith the adenine of cAMP. Structural comparison between isoform PDE4D2-cAMP and PDE10A2-cAMP shows an anti configuration of cAMP in PDE4, but syn in PDE10
-
hanging drop method, PDE4D2 in complex with the nonselective inhibitor 3-isobutyl-1-methylxanthine
-
hanging-drop vapor-diffusion method, crystal structures of the catalytic domain of phosphodiesterase 4B complexed with AMP (2.0 A), 8-Br-AMP (2.13 A), and rolipram (2.0 A)
-
in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4A, PDE4B, PDE4C. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. Detailed structural comparison; in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4A, PDE4C, PDE4D. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same resiudues in each instance. Detailed structural comparison; in complex with inhibitor 4-[8-(3-nitrophenyl)-[1,7]naphthyridin-6-yl]benzoic acid, comparison with isoforms PDE4B, PDE4C, PDE4D. Inhibitor binds in the same conformation to the deep cAMP substrate pocket and interacts with the same residues in each instance. Detailed structural comparison; unliganded, detailed structural comparison with isoforms PDE4A, PDE4B, PDE4C
P27815, Q08499
molecular dynamics simulations. The second bridging ligand in the active site is HO- rather than H2O, serving as a nucleophile to initialize the catalytic hydrolysis of cAMP
-
NMR and CD analysis of the N-terminal 38mer peptide of isoform PDE4D5 which contains the entire signaling scaffold protein RACK1 interaction domain together with a portion of the beta-arrestin binding site. The peptiode has a distinct amphipathic helical structure. Study on binding to RACK1 and to beta-arrestin
-
unliganded PDE8A1 and in complex with 3-isobuytl-1-methylxanthine, hanging drop vapour diffusion method, using 100 mM sodium cacodylate (pH 6.5), 15% 2-propanol, 30% ethylene glycol, and 8-10% PEG3350 at 4C
-
pH STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
6 - 7
-
PdeB shows no 3',5'-cAMP phosphodiesterase activity at or below pH 6.0, PdeA and PdeB activities are strongly inhibited by 0.1 M sodium phosphate buffer (pH 6.0 and 7.0)
692369
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
50 - 55
-
heat treatment at 50C or 55C for 5 min slightly activates the phosphodiesterase activity of PdeB against 3',5'-cAMP by about 1.2fold of the control while PdeA activity is not activated by the heat treatment
692369
55
-
soluble HSPDE4A10 is more thermostable (T0.5: 11 min) than the particulate enzyme (T0.5: 5 min)
689068
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
Ca2+ required for stability
Q309F4
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
anion exchange chromatography
-
partially purified by Q-Sepharose column chromatography
-
ammonium sulfate fractionation and amylose-resin column chromatography
-
from inclusion bodies
-
gel filtration
-
Ni-NTA column chromatography
-
Talon CellThru column chromatography, gel filtration
-
Ni-NTA column chromatography and Sephacryl S-200 gel filtration; recombinant His-tagged enzyme from Escherichia coli strain M15(pREP4) by nickel affinity chromatography
D4P095
GST-rPDE4D1 fusion protein
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
baculovirus-expressed PDE4 in Sf9 cells; baculovirus-expressed PDE7 in Sf9 cells
-
the DdPDE4 catalytic domain (amino acids 264-771) is expressed in vegetative AX2 cells
Q86H13
cloned and expressed in Sf9 cells with recombinant baculovirus infection
-
Epac1-camps-PDE4A1 fusion protein is expressed in HEK-293 cells
-
expressed in COS1 cells
-
expressed in Escherichia coli strain BL21
-
expressed in transfected COS7 cells. The human PDE4A species, h6.1 (HSPDE4A4C), which lacks the N-terminal extension of PDE-46, is an entirely soluble species when expressed in COS7 cells
-
expression in baculovirus transfected Sf9 cells
-
expression in COS-7 cell; When expressed in COS-7 cells, PDE4A8 localizes predominantly in the cytosol, but 20% of the enzyme was associated with membrane fractions
P27815
expression in Escherichia coli as N-terminal glutathione S-transferase-fusion protein
-
expression in Sf9 insect cells
Q9NP56
expression in Spodoptera frugiperda
-
expression of the catalytic domain in Escherichia coli
-
recombinant PDE7B expressed in transfected COS-7 cells
-
the catalytic domain of human PDE4D is cloned from HL-60 cells and expressed in Escherichia coli JM109 cells
-
transient expression of the engineered human PDE4A10 open reading frame in COS7 cells allows detection of a 121000 Da protein in both soluble and particulate fractions. PDE4A10 is localized primarily to the perinuclear region of COS7 cells
-
expression in Escherichia coli; expression in Escherichia coli
Q6S996, Q6S997
-
O88502
;
O89084, Q9QXI7
expressed in Neuro-2A and NIH-3T3 cells
B1PSD9
expressed in Schizosaccharomyces pombe
-
expression in Sf9 insect cells
-
PDE7B protein is expressed in a baculovirus expression system; PDE7B protein is expressed in a baculovirus expression system
P70453
expressed in Escherichia coli BL21 cells
-
expressed in Escherichia coli M15(pREP4) cells; gene cpdA, DNA and mino acid sequenc determination and analysis, expression of His-tagged enzyme in Escherichia coli strain M15(pREP4)
D4P095
-
P14270, P14646
cells of two human follicular thyroid carcinoma cell lines (FTC133, FTC236) are stably transfected with a cDNA encoding the PDE4A cAMP-specific phosphodiesterase (PDE) splice variant RD1 (RNPDE4A1A) so as to generate the cloned cell lines, FTC133A and FTC236A
-
expressed in COS-1 cells
-
expressed in HEK-293 cells
-
expressed in Rattus norvegicus INS-1 832/13 cell line
-
expression in COS1 cells
-
expression in COS7 cells
-
expression of PDE4B4 cDNA in COS7 cells. Treatment of COS7 cells with forskolin, to elevate cAMP levels, produced activation of PDE4B4, which is associated with the phosphorylation of PDE4B4 on Ser56 within UCR1
P14646
full coding sequence of the phosphodiesterase PDE4D1 is inserted in the bacterial expression vector pGEX-KG. N- and C-terminal truncations are also placed in the same vector, allowing the expression and purification of glutathione S-transferase (GST)-PDE fusion proteins using glutathione-Sepharose
-
TbPDE1 is expressed in Saccharomyces cerevisiae at levels that are sufficient to produce a clear phenotype (heat-shock resistance, growth as a smooth suspension), but that are too low to be detectable in PDE assay of cell lysates. The N-terminally truncated construct pET-PDE1-(Arg189-Thr620) is expressed in Escherichia coli as an active enzyme
-
expression in Escherichia coli
Q4ZHU6
expression in Saccharomyces cerevisiae
Q309F4
expression of TcrPDEB1 catalytic domain in Escherichia coli
Q49UB9
expressed in Escherichia coli
Q846Z1
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
2fold increased PDE7B mRNA expression in chronic lymphocytic leukemia correlates with a 10fold higher expression of PDE7B protein and results in an increased contribution of PDE7 to total PDE activity
-
isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
-
the cAMP-dependent transcription factor Vfr directly activates expression of cpdA in response to elevated intracellular cAMP
D4P095
cpdA expression is positively regulated by cAMP-Vfr. cAMP-Vfr binds to the cpdA promoter region, suggesting that in vivo, cpdA transcription is directly activated by cAMP-Vfr
D4P095
isoforms PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A show an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). mRNA expression of isoforms PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A does not change with age
-
forskolin treatment alone is unable to stimulate mAKAP-bound PDE4D3 activity significantly in HEK-293 cells, whereas forskolin (0.05 mM) and okadaic acid (0.3 mM) treatment together synergistically increase PDE4D3 activity
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A590C
-
mutation has no significant influence on substrate affinity or specificity
D440A
-
unlike wild type enzyme, the mutant enzyme shows activity with cGMP
D440N
-
unlike wild type enzyme, the mutant enzyme shows activity with cGMP
F484Y
-
mutation has no significant influence on substrate affinity or specificity
H305P
O95263
the mutation is associated with micronodular adrenocortical disease
L391A
-
mutation has no significant influence on substrate affinity or specificity
P595I
-
mutation leads to 7fold decrease of substrate affinity and an 14fold decrease of the affinity towards the PDE4-specific inhibitor rolipram
T748F
-
the mutation increases the PDE8A1 sensitivity to several nonselective or family selective PDE inhibitors, the catalytic efficiency of the mutant is about 2fold better than that of the wild type PDE8A1
V501A
-
mutation has no significant influence on substrate affinity or specificity
W375Q
-
mutation abolishes catalytic activity
W605I
-
mutation abolishes catalytic activity
W605V
-
mutation abolishes catalytic activity
D63A
D4P095
the mutant shows less than 0.1% of wild type CpdA activity
H23A
D4P095
the mutant shows less than 0.1% of wild type CpdA activity
D448N
-
mutation in conserved active site residue, loss of enzyme function does not affect steady-state acetylcholine release or reception
additional information
Q86H13
enzyme knock-out strains show normal aggregation but impaired development from the mound stage on
W605Y
-
mutation abolishes catalytic activity
additional information
D0ERY7, D0ERY8
generation of gene-deletion mutants of the high-affinity PdeH cAMP phosphodiesterase, phenotypes, overview
additional information
D0ERY7, D0ERY8
generation of gene-deletion mutants of the low-affinity PdeL cAMP phosphodiesterase, phenotypes, overview
H305P
-
the mutation is associated with micronodular adrenocortical disease
additional information
-
generation of PDE8B KO mice, that show elevated levels of urinary corticosterone in both basal and stressed conditions compared with their littermate wild-type controls
N93A
D4P095
the mutant shows less than 0.1% of wild type CpdA activity
additional information
Q38F42, Q38F46, Q8WQX9
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
Q38F42, Q38F46, Q8WQX9
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
additional information
Q309F4
isoform PDEA1 is able to complement a yeast strain deficient in phosphodiesterase genes
Renatured/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
refolding is initiated by addition of 0.03 mg/ml protein to a buffer of 0.5 M Tris-HCl pH 7.0, 20 mM MgCl2, 20 mM MnCl2, 0.020 mM ZnSO4, 0.7 M arginine, 30% glycerol, 10 mM NaCl, 1 mM KCl, and 10 mM dithiothreitol, at 4C for three days
-
refolding to active enzyme from inclusion bodies requires high concentrations of arginine hydrochloride, ethylene glycol, and magnesium chloride at pH 8.5
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
-
enzyme variants PDE4B and/or PDE4D regulate cell growth through cAMP targets in the HMG malignant melanoma cell
medicine
-
expression of phosphodiesterases PDE1A, PDE1C, PDE3B, and PDE5A is enhanced in pulmonary arterial smooth muscle cells from both patients with idiopathic pulmonary arterial hypertension or secondary pulmonary hypertension compared with control. Increase in phosphodiesterase isoforms, particularly in PDE1C, contributes to decreased cAMP levels and increased proliferation of pulmonary arterial smooth muscle cells in patients with pulmonary hypertension
medicine
-
interactions of PDE4D5 with both the N- and C-terminal domains of beta-arrestin are essential for beta2-adrenoceptor regulation
medicine
-
reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells
medicine
-
statistically significnat differences between cAMP-dependent phosphodiesterase activity in benign tumours and healthy control. Enzymatic activity in tumour groups analysed such as Warthin's tumour, pleomorphic adenoma. Or myoepithelioma, is about 50% lower than in control
medicine
-
isoform PDE7B is a drug target in chronic lymphocytic leukemia
medicine
-
PDE5 inhibition is a efficacious oral therapy for erectile dysfunction
medicine
-
phosphodiesterase 4B mediates Streptococcus pneumoniae-induced mucin gene MUC5AC up-regulation by inhibiting the expression of a negative regulator MKP-1, which in turn leads to enhanced MAPK ERK activation and subsequent up-regulation of MUC5AC. PDE4B inhibits MKP-1 expression in a cAMP-PKA-dependent manner. PDE4-specific inhibitor rolipram inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation both in vitro and in vivo. PDE4B plays a critical role in MUC5AC induction. Topical and post-infection administration of rolipram into the middle ear potently inhibits Streptomyces pneumoniae-induced MUC5AC up-regulation
molecular biology
-
development of cell-permeable peptide reagents based upon the N-terminal region of PDE4D5 that allow for the selective disruption of PDE4D5 targeting to specific signalling scaffolds, namely beta-arrestin and RACK1
medicine
-
PDE4 may be of particular importance as an antidepressant target in that it is regulated by repeated treatment with both norepinephrine and serotonin reuptake inhibitors as well as by the PDE4 inhibitor rolipram
medicine
-
reactive oxygen-species mediated lung inflammation may be mediated at least in part by calcium and elevated enzyme activity associated with decreased caMP in both macorphages and epithelial cells
medicine
-
PDE5 inhibition improved short-term object recognition performance after an acute tryptophan depletion induced deficit
molecular biology
-
convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE4, convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE7, convenient and sensitive radioenzymatic assay for characterization and determining the contribution if the various PDE families in cell and tissue, PDE8
medicine
Q38F42, Q38F46, Q8WQX9
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB1, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
medicine
Q38F42, Q38F46, Q8WQX9
enzyme knock-down by RNAi reveals that it may be complemented by isoform PDEB2, but simultaneous ablation of PDEB1 and PDEB2 leads to cell death in bloodstream form trypanosomes. In vivo application of RNAi completely prevents infection and eliminates ongoing infections
medicine
-
TbrPDEB1 and TbrPDEB2 are essential for virulence, making them valuable potential targets for new PDE-inhibitor based trypanocidal drugs