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Information on EC 3.1.4.17 - 3',5'-cyclic-nucleotide phosphodiesterase
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3.1.4.17 3',5'-cyclic-nucleotide phosphodiesteraseIUBMB Comments
Acts on 3',5'-cyclic AMP, 3',5'-cyclic dAMP, 3',5'-cyclic IMP, 3',5'-cyclic GMP and 3',5'-cyclic CMP.
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Word Map
- 3.1.4.17
- phosphodiesterases
- adenylate
- rolipram
-
camp-dependent
- pka
- forskolin
- guanosine
- ibmx
- theophylline
- platelet
- prostaglandin
-
adenylyl
- milrinone
- isoproterenol
- adipocytes
- cilostazol
- 3-isobutyl-1-methylxanthine
-
schizophrenia
- striatal
-
vasodilator
-
inotropic
-
lipolysis
- papaverine
- zaprinast
- 3',5'-monophosphate
- dictyostelium
-
glucanase
- sildenafil
- trifluoperazine
-
beta-adrenergic
-
camp-mediated
- dipyridamole
-
guanylyl
-
cardiotonic
-
spiny
-
bronchodilator
- amrinone
- isobutylmethylxanthine
- laminarin
-
low-km
- isoprenaline
- methylxanthines
-
antilipolytic
- ehna
- medicine
- beta-1,3-glucanases
- claudication
- aminophylline
- tadalafil
- molecular biology
- roflumilast
-
ca2+-calmodulin
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota
Synonyms
cyclic nucleotide phosphodiesterase, camp phosphodiesterase, pde4d, pde10a, pde3b, pde3a, camp-pde, pde2a, phosphodiesterase 3, pde11a, 
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
3',5'-cyclic nucleoside monophosphate phosphodiesterase
-
-
-
-
3',5'-cyclonucleotide phosphodiesterase
-
-
-
-
3',5'-nucleotide phosphodiesterase
-
-
-
-
3':5'-CNP
-
-
-
-
3':5'-cyclic nucleotide 5'-nucleotidohydrolase
-
-
-
-
61 kDa Cam-PDE
-
-
-
-
63 kDa Cam-PDE
-
-
-
-
Cam-PDE 1A
-
-
-
-
Cam-PDE 1B
-
-
-
-
Cam-PDE 1C
-
-
-
-
CGB-PDE
-
-
-
-
CGIP1
-
-
-
-
CGIPDE1
-
-
-
-
cGMP-binding cGMP-specific phosphodiesterase
-
-
-
-
CGS-PDE
-
-
-
-
cGSPDE
-
-
-
-
CpdA
cyclic 3',5'-mononucleotide phosphodiesterase
-
-
-
-
cyclic 3',5'-nucleotide phosphodiesterase
-
-
-
-
cyclic 3',5'-phosphodiesterase
-
-
-
-
cyclic 3',5-nucleotide monophosphate phosphodiesterase
-
-
-
-
Cyclic GMP stimulated phosphodiesterase
-
-
-
-
cyclic nucleotide phosphodiesterase
DPDE1
-
-
-
-
DPDE2
-
-
-
-
DPDE3
-
-
-
-
DPDE4
-
-
-
-
dual-specificity PDE
Dunce protein
-
-
-
-
GMP-PDE alpha
-
-
-
-
GMP-PDE beta
-
-
-
-
GMP-PDE delta
-
-
-
-
GMP-PDE gamma
-
-
-
-
HCP1
-
-
-
-
High-affinity cAMP phosphodiesterase
-
-
-
-
Learning/ memory process protein
-
-
-
-
Low-affinity cAMP phosphodiesterase
-
-
-
-
MMPDE8
-
-
-
-
nucleoside 3',5'-cyclic phosphate diesterase
-
-
-
-
nucleoside-3',5-monophosphate phosphodiesterase
-
-
-
-
p17 protein
-
-
-
-
P2A
-
-
-
-
PDE V-B1
-
-
-
-
PDE V-C1
-
-
-
-
PDE1
PDE10
PDE10A
PDE11
PDE11A
PDE1A
PDE1B
PDE1C
PDE2
PDE21
-
-
-
-
PDE2A
PDE3
PDE32
-
-
-
-
PDE3A
PDE3B
PDE43
-
-
-
-
PDE46
-
-
-
-
PdeA
PDEase
-
-
-
-
PDEase regA
-
-
-
-
PdeB
phosphodiesterase 1
phosphodiesterase 2
phosphodiesterase type 3A
phosphodiesterase, cyclic 3',5'-nucleotide
-
-
-
-
TM1595
TM22
-
-
-
-
cyclic nucleotide phosphodiesterase
-
-
-
-
PDE10A
-
hydrolyses both 3',5'-cAMP and 3',5'-cGMP although with different kinetic parameters
PDE10A
-
hydrolyses both 3',5'-cAMP and 3',5'-cGMP although with different kinetic parameters
PdeA
-
has 3',5'- and 2',3'-cAMP phosphodiesterase and phosphomonoesterase activities
PdeB
-
has 3',5'- and 2',3'-cAMP phosphodiesterase and phosphomonoesterase activities
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
-
-
-
-
nucleoside 3',5'-cyclic phosphate + H2O = nucleoside 5'-phosphate
mechanism
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
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SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-nucleotide 5'-nucleotidohydrolase
Acts on 3',5'-cyclic AMP, 3',5'-cyclic dAMP, 3',5'-cyclic IMP, 3',5'-cyclic GMP and 3',5'-cyclic CMP.
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CAS REGISTRY NUMBER
COMMENTARY
9040-59-9
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2',3'-cAMP + H2O
3'-AMP
-
in PdeB the phosphodiesterase activity for 2',3'-cAMP is about 1.7fold higher than that for 3',5'-cAMP
-
-
?
cAMP + H2O
5'-AMP
-
degradation of extracellular cAMP by isoforms PDE1, PDE7. Degradation of intracellular cAMP by isoform PDE2
-
-
?
cGMP + H2O
5'-GMP
-
degradation of intracellular cGMP by isoform PDE3
-
-
?
UDP-D-glucose + H2O
?
-
UDP-D-glucose is hydrolyzed by PdeB, but not by PdeA
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE1
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE11
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
inhibition of cAMP hydrolysis by cGMP is likely to contribute to cGMP-mediated signaling in myocardium
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE11
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE2
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
activity with 3',5'-cGMP is higher than with 3',5'-cAMP
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
maximal velocity for cAMP is 4fold to 10fold higher than for cGMP, PDE11A4
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
3',5'-cAMP is completely hydrolyzed to adenosine when incubated with PdeA for a prolonged time
-
-
?
3',5'-cAMP + H2O
5'-AMP
-
-
-
-
?
3',5'-cAMP + H2O
5'-AMP
the enzyme is preferentially degrading linear dinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates
-
-
?
3',5'-cAMP + H2O
5'-AMP
the enzyme is preferentially degrading linear dinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE1
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
specific for 3',5'-cGMP and 3',5'-cAMP, PDE11
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE11
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
activity with 3',5'-cGMP and 3',5'-cAMP is nearly identical, PDE2
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
activity with 3',5'-cGMP is higher than with 3',5'-cAMP
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
maximal velocity for cAMP is 4fold to 10fold higher than for cGMP, PDE11A4
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
PDE1 and PDE2 are the main PDEs that act to degrade cGMP in methacholine-stimulated cells
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
-
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
the technique can be used to measure Ca2+/CaM-stimulated PDE activity in cultured cells or tissues
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
?
additional information
?
-
-
muscarinic antagonists acting possibly as inverse agonists on M2/M3 muscarinic acetylcholine receptors anchored to sarcolemma membranes can initiate a new signal transducing cascade leading to inhibition of PDEI, which produces a simultaneous rise in both cAMP and cGMP intracellular levels in tracheal smooth muscle
-
-
-
additional information
?
-
-
real-time monitoring of PDE2 activity by a fluorescent cAMP sensor shows that activation of PDE2 results in a rapid decrease of intracellular cAMP from high micromolar to sub-micromolar range within a few seconds. High catalytic activity and fast action in regulating cAMP signaling in a physiological system
-
-
-
additional information
?
-
-
isoforms PDE1 and PDE7 are dual-specificity enzymes with negative cooperativity and very different kinetics. Both have 2-3fold lower affinity for cGMP than for cAMP
-
-
-
additional information
?
-
-
h-prune activity is suppressed by dipyridamole and enhanced by the interaction with nm23-H1. Activity is involved in promoting cancer metastasis
-
-
-
additional information
?
-
-
the enzyme might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels
-
-
-
additional information
?
-
-
isoform PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists
-
-
-
additional information
?
-
-
the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial cells
-
-
-
additional information
?
-
-
splice variants PDE11A1 and PDE11A2 show higher affinity for cAMP and cGMP than PDE11A4
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
additional information
?
-
-
structure analysis of phosphodiesterase 10 binding with cAMP and cGMP by hybrid quantum mechanical/molecular mechanical calculations using cyrstal structures of the substrate-bound enzyme, detailed overview
-
-
-
additional information
?
-
-
PDE2 can hydrolyze both cAMP and cGMP with similar maximal rates. PDE1A prefers cGMP, PDE1B cAMP, and PDE1C hydrolyzes both substrates equally. The PDE3 family can hydrolyze both cAMP and cGMP
-
-
-
additional information
?
-
-
PDE1 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
PDE1A_v7 is the major form of cyclic nucleotide phosphodiesterase 1A expressed in mature sperm and is therefore likely to play an important role in cyclic nucleotide regulation of mature sperm function
-
-
-
additional information
?
-
isoform PDE2 regulates the basal cGMP concentration in thalamic neuron
-
-
-
additional information
?
-
-
Rv0805 protein could have an important role to play in regulating cAMP levels in Mycobacterium tuberculosis
-
-
-
additional information
?
-
-
3',5'-cGMP is either not hydrolysed or is cleaved very slowly by PdeA and PdeB, PdeA and PdeB show no activities toward 2'-AMP and 2'-GMP
-
-
-
additional information
?
-
-
PdeA and PdeB 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
-
-
-
additional information
?
-
-
substrate specificity of PdeE, overview
-
-
-
additional information
?
-
-
PDE1A is involved in cGMP breakdown in parotid acinar cells of Oryctolagus cuniculus
-
-
-
additional information
?
-
-
insulin-induced activation of the membrane bound PDE3B is a key step in insulin-mediated inhibition of lipolysis and is also involved in the regulation of insulin-mediated glucose uptake and lipogenesis in adipocytes
-
-
-
additional information
?
-
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
cytoplasmic isoform PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas nuclear enzyme isoform PDE1A is important in vascular smoth muscle cell growth and survival
-
-
-
additional information
?
-
-
PDE10A regulates both cAMP and cGMP signaling cascades to impact early signal processing in the corticostriatothalamic circuit
-
-
-
additional information
?
-
enzyxme displays dual specificity for hydrolysis of both cAMP and cGMP
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
additional information
?
-
the enzyme is preferentially degrading linear dinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates
-
-
-
additional information
?
-
-
the enzyme is preferentially degrading linear dinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates
-
-
-
additional information
?
-
the enzyme is preferentially degrading linear dinucleotides, such as 5'-pApA, 5'-pGpG, and 5'-pApG, compared with cyclic dinucleotide substrates
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
3',5'-cAMP + H2O
5'-AMP
-
inhibition of cAMP hydrolysis by cGMP is likely to contribute to cGMP-mediated signaling in myocardium
-
-
?
3',5'-cGMP + H2O
5'-GMP
-
PDE1 and PDE2 are the main PDEs that act to degrade cGMP in methacholine-stimulated cells
-
-
?
nucleoside 3',5'-cyclic phosphate + H2O
nucleoside 5'-phosphate
-
-
-
-
?
additional information
?
-
-
muscarinic antagonists acting possibly as inverse agonists on M2/M3 muscarinic acetylcholine receptors anchored to sarcolemma membranes can initiate a new signal transducing cascade leading to inhibition of PDEI, which produces a simultaneous rise in both cAMP and cGMP intracellular levels in tracheal smooth muscle
-
-
-
additional information
?
-
-
real-time monitoring of PDE2 activity by a fluorescent cAMP sensor shows that activation of PDE2 results in a rapid decrease of intracellular cAMP from high micromolar to sub-micromolar range within a few seconds. High catalytic activity and fast action in regulating cAMP signaling in a physiological system
-
-
-
additional information
?
-
-
h-prune activity is suppressed by dipyridamole and enhanced by the interaction with nm23-H1. Activity is involved in promoting cancer metastasis
-
-
-
additional information
?
-
-
the enzyme might be involved in multiple physiological processes in various organs via its ability to modulate intracellular cAMP and cGMP levels
-
-
-
additional information
?
-
-
isoform PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists
-
-
-
additional information
?
-
-
the effect of increasing concentrations of cGMP on endothelial permeability is biphasic, attributable to the relative amounts of enzyme isoforms PDE2A and PDE3A in endothelial cells
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
additional information
?
-
-
structure analysis of phosphodiesterase 10 binding with cAMP and cGMP by hybrid quantum mechanical/molecular mechanical calculations using cyrstal structures of the substrate-bound enzyme, detailed overview
-
-
-
additional information
?
-
-
PDE1 in Pukinje neurons may play a role in limiting the cGMP-mediated long-term depression response
-
-
-
additional information
?
-
Q61481
PDE1A_v7 is the major form of cyclic nucleotide phosphodiesterase 1A expressed in mature sperm and is therefore likely to play an important role in cyclic nucleotide regulation of mature sperm function
-
-
-
additional information
?
-
Q01065
isoform PDE2 regulates the basal cGMP concentration in thalamic neuron
-
-
-
additional information
?
-
-
Rv0805 protein could have an important role to play in regulating cAMP levels in Mycobacterium tuberculosis
-
-
-
additional information
?
-
-
PDE1A is involved in cGMP breakdown in parotid acinar cells of Oryctolagus cuniculus
-
-
-
additional information
?
-
-
insulin-induced activation of the membrane bound PDE3B is a key step in insulin-mediated inhibition of lipolysis and is also involved in the regulation of insulin-mediated glucose uptake and lipogenesis in adipocytes
-
-
-
additional information
?
-
Q01062
cGMP levels in the spinal cord are controlled by a number of enzyme isoforms, that can be present in the same cell. Role of NO-cGMP signaling in nociceptive processing
-
-
-
additional information
?
-
-
cytoplasmic isoform PDE1A regulates myosin light chain phosphorylation with little effect on apoptosis, whereas nuclear enzyme isoform PDE1A is important in vascular smoth muscle cell growth and survival
-
-
-
additional information
?
-
-
PDE10A regulates both cAMP and cGMP signaling cascades to impact early signal processing in the corticostriatothalamic circuit
-
-
-
additional information
?
-
-
PDE3A physically and functionally interacts with cystic fibrosis transmembrane conductance regulator, CFTR, channel
-
-
-
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
CaCl2
-
entirely dependent on the presence of divalent cations, activity with 0.2 mM CaCl2 is 15.9% of maximal activity obtained with 2 mM MgCl2
Co2+
Fe3+
Mg2+
Mn2+
Zn2+
additional information
Ca2+
-
differential effect on isozymes, activation only in complex with calimodulin, overeview
Ca2+
-
differential effect on isozymes, activation only in complex with calimodulin, overeview
Co2+
-
the enzyme activities of PdeA and PdeB in the hydrolysis of 3',5'-cAMP are stimulated 3.2fold and 1.98fold at pH 8.0 in 50 mM Tris-HCl buffer by the addition of Co2+ at 0.05 mM, respectively
Mg2+
-
is coordinated to Asp564, two phosphate oxygen atoms, and three water molecules
Mg2+
-
entirely dependent on the presence of divalent cations, maximal activity with 2 mM MgCl2
Mn2+
-
Km value and Hill constant for wild-type 0.021 mM and 1, respectively, for mutant D21A 0.021 mM and 4.1, respectively, for mutant H23A 0.053 mM and 1, respectively, for mutant D66A, 0.072 and 6.4, respectively, for mutant H169A 0.022 and 1.7, respectively, for mutant H207A, 0.062 and 3.1, respectively
Mn2+
-
the enzyme activities of PdeA and PdeB in the hydrolysis of 3',5'-cAMP are stimulated 4fold and 2.14fold at pH 8.0 in 50 mM Tris-HCl buffer by the addition of Mn2+ at 0.05 mM, respectively
Mn2+
-
entirely dependent on the presence of divalent cations, activity with 2 mM MnCl2 is 53.5% of maximal activity obtained with 2 mM MgCl2
Zn2+
-
is coordinated to His529, His563, Asp564, Asp674, and two phosphate oxygen atoms
Zn2+
-
entirely dependent on the presence of divalent cations, activity with 0.03 mM ZnCl2 is 19.5% of maximal activity obtained with 2 mM MgCl2
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.0001 mM, PDE3A; IC50: 0.00028 mM, PDE3B
(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: 0.000006 mM, PDE3; IC50: 0.0012 mM, PDE2; IC50: 0.015 mM, PDE1
(6aS,9aR)-3-benzyl-2-(biphenyl-4-ylmethyl)-5-methyl-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[2,1-b]purin-4(3H)-one
-
comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
(Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate
-
time-dependent and irreversible inactivation of PDE3A
1-(2-methylbenzyl)-7-(2-oxopropyl)-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-(4-chlorobenzyl)-7-(2-oxopropyl)-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
-
-
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
IC50: 0.00000034 mM, PDE3A, highly selective PDE3 inhibitor; IC50: 0.0000019 mM, PDE3B; IC50: 0.0.0209 mM, PDE2; IC50: 0.1129 mM, PDE1
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
3'-benzyl-2'-(biphenyl-4-ylmethyl)-5'-methyl-3'H-spiro[cyclopentane-1,7'-imidazo[2,1-b]purin]-4'(5'H)-one
-
comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
3-isobutyl-8-(methoxymethyl)-1-methyl-3,9-dihydro-1H-purine-2,6-dione
-
i.e. 8MM-IBMX, comparison of inhibitory effect on several recombinant human PDE isoforms
5-(3-cyclopentyloxy-4-methoxy-phenyl)-pyrrolidin-2-one
-
50% inhibition at about 0.1 mM
5-methyl-2-[4-(trifluoromethyl)benzyl]-5,6a,7,8,9,9a-hexahydrocyclopenta[4,5]imidazo[2,1-b]purin-4(1H)-one
-
i.e. SCH51866, comparison of inhibitory effect on several recombinant human PDE isoforms. Effective PDE1 inhibitor in cellular context
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
IC50: 0.00000032 mM, PDE3A, highly selective PDE3 inhibitor; IC50: 0.0000015 mM, PDE3B; IC50: 0.0429 mM, PDE1; IC50: 0.0523 mM, PDE2
8-methoxymethyl-isobutylmethylxanthine
-
inhibits activated PDE1 and PDE2 isoforms as well as PDE4 and PDE5, is 3times more potent in inhibiting PDE5 than PDE1
apigenin
-
IC50: 0.0105 mM, PDB3; IC50: 0.0167 mM, PDB2; IC50: 0.0254 mM, PDB1
BAY60-7550
inhibition of isoform PDE2, results in increase in basal cGMP levels after application to thalamic neurons
ethylene glycobis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
soluble but not particulate form
-
genistein
-
IC50: 0.0017 mM, PDB2; IC50: 0.0129 mM, PDB3; IC50: 0.0168 mM, PDB1
luteolin
-
IC50: 0.0101 mM, PDB3; IC50: 0.0133 mM, PDB2; IC50: 0.0215 mM, PDB1
myricetin
-
IC50: 0.0124 mM, PDB3; IC50: 0.0128 mM, PDB2; IC50: 0.0249 mM, PDB1
N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide
-
soluble but not particulate form
orthovanadate
-
PdeA shows 26% relative activity and PdeB shows 29% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM orthovanadate
phosphate
-
PdeA and PdeB enzyme activities are strongly inhibited by 0.1 M sodium phosphate buffer (pH 6.0 and 7.0), the PdeB activity is more strongly inhibited by 0.1 M phosphate than is PdeA activity
phosphoserine
-
PdeA shows 59% relative activity and PdeB shows 73% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM phosphoserine
phosphotyrosine
-
PdeA shows 44% relative activity and PdeB shows 52% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM phosphotyrosine
quinazolinamine
-
IC50: 0.01 mM, PDE3; IC50: 0.23 mM, PDE1; IC50: 0.241 mM, PDE2
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
potent inhibitor
-
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
-
selective PDE10A inhibitor, inhibition of striatal PDE10A activity increases the responsiveness of medium-sized spiny projection neurons to depolarising stimuli
-
3-isobutyl-1-methylxanthine
-
broad-spectrum PDE inhibitor; broad-spectrum PDE inhibitor; broad-spectrum PDE inhibitor
8-methoxymethyl-3-isobutyl-1-methylxanthine
-
0.02 mM selectively inhibits PDE1; 0.02 mM selectively inhibits PDE1
Cilostamide
-
IC50: 0.000027 mM, PDE3A; IC50: 0.00005 mM, PDE3B; IC50: 0.0125 mM, PDE2
Cilostamide
-
IC50: 0.00013 mM, PDE3; IC50: 0.048 mM, PDE2; IC50: 0.221 mM, PDE1
cilostazol
-
IC50: 0.0002 mM, PDE3A; IC50: 0.00038 mM, PDE3B; IC50: 0.0452 mM, PDE2
dioclein
-
potent selective and calmodulin-independent inhibitor of PDE1, competitive inhibitor for cGMP hydrolysis by PDE1 in basal-activated (1 mM EGTA) and calmodulin-activated (18 nM calmodulin with 0.01 mM CaCl2) states. Dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 11fold more selective for the activated PDE1 isoform compared to basal PDE2 (70fold), activated PDE2 (26fold), PDE3 (19fold), PDE4 (11fold), and PDE5 (16fold)
dioclein
-
dioclein is at least 11times more potent in inhibiting calmodulin-activated PDE1 than other PDE types. Among PDE1-PDE5, dioclein is at least 11fold more selective for the activated PDE1 isoform compared to basal PDE2 (70fold), activated PDE2 (26fold)
EDTA
-
PdeA and PdeB show 39% relative activity in the hydrolysis of 3',5'-cAMP in the presence of 0.05 mM EDTA
erythro-9-(2-hydroxy-3-nonyl)adenine
inhibition of isoform PDE2, results in increase in basal cGMP levels after application to thalamic neurons
quercetin
-
IC50: 0.0056 mM, PDB3; IC50: 0.0179 mM, PDB2; IC50: 0.0278 mM, PDB1
sildenafil
-
IC50: IC50: 0.00012 mM, PDE11; IC50: IC50: 0.0013 mM, PDE1
sildenafil
-
IC50: 3800 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
tadalafil
-
PDE11 inhibition has impacts on sperm quality. Reasonable caution should by suggested in patients taking the prescribed dosages of tadalafil, a PDE5 inhibitor which could crossreact with human PDE11A splicing variants
tadalafil
-
IC50: 73 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
vardenafil
-
IC50: 840 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
vinpocetine
-
comparison of inhibitory effect on several recombinant human PDE isoforms
Zn2+
-
PdeA and PdeB are potently inhibited in the hydrolysis of 3',5'-cAMP by 0.05 mM Zn2+ with 24% and 28% of remaining activity
additional information
-
IC50 for vardenafil, sildenafil and tadalafil is above 10000 nM, PDE2
-
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, which is prevented by inhibition of enzyme isoform PDE1. Inhibition of both isoforms PDE1 and PDE4 completely prevent the t-butylhydroperoxide stimulated TNF-alpha release
-
additional information
-
PdeA and PdeB are not stimulated by 3-isobuthyl-1-methylxanthine, theophylline, beta-glycerophosphate, Ca2+, Mg2+, Fe2+, and Fe3+
-
additional information
-
the broad-spectrum phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine, IBMX, has no effect on the activity of PdeE at 1 mM. No inhibition by theophylline at 1 mM, beta-glycerophosphate at 0.1 mM, and by orthovanadate
-
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
clozapine
-
chronic treatment with 20 mg/kg clozapine increases PDE10A expression by 62%
haloperidol
-
chronic treatment with 1 mg/kg haloperidol increases PDE10A expression by 118%; chronic treatment with 1 mg/kg haloperidol increases PDE10A expression by 65%
lipopolysaccharide
-
expression and activity of isoforms PDE2, PDE3, PDE11 in cultured peritoneal macrophages are recovered after treatment of cultured cells with lipopolysaccharide. Lipopolysaccharide also up-regulates enzyme expression in resident peritoneal macrophages
Calmodulin
-
differential effect on isozymes, activation only in complex with Ca2+, overview
Calmodulin
-
differential effect on isozymes, activation only in complex with Ca2+, overview
cGMP
-
binding of cGMP to GAF domains within PDE2 results in the activation of all PDE2 variants
ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
activation
ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid
-
reverses Ca2+ inhibition
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0038
2',3'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.0052
2',3'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.0033
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.005
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.032
3',5'-cAMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
0.034
3',5'-cGMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
additional information
additional information
-
biphasic behaviour with 3',5'-cAMP as substrate
-
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0006
2',3'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.00096
2',3'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.00093
3',5'-cAMP
-
PdeB, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.00096
3',5'-cAMP
-
PdeA, in 50 mM Tris-HCl, pH 8.0, 0.05 mM MnCl2, at 40°C
0.3
3',5'-cAMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
4.2
3',5'-cGMP
-
catalytic domain of PDE2A (PDE2A residues 578-919), enzyme expressed in Escherichia coli
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kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
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Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000062
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
-
0.0434
(Rp)-guanosine-3',5'-cyclic-S-(4-bromo-2,3-dioxobutyl)monophosphorothioate
-
in 45 mM HEPES (pH 7.2), 20 mM MgCl2, and 4 mM MES, at 25°C
0.0000003
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
-
-
0.0003
5-(2-propoxyphenyl)-2,3-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
-
0.00000022
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
-
-
0.00055
dioclein
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.00062
dioclein
-
isoform PDE1 in calmodulin-activated state, pH and temperature not specified in the publication
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IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0001 - 0.00028
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
0.0023
(2S,3R)-3-(7-amino-3H-imidazo[4,5-b]pyridin-3-yl)nonan-2-ol
Homo sapiens
-
isoform PDE2, pH and temperature not specified in the publication
0.000006 - 0.015
(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
0.053
1-(2-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0095
1-(3-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0007
1-(4-chlorobenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.0015
1-(4-methylbenzyl)-7-(2-oxopropyl)-3-propyl-3,7-dihydro-1H-purine-2,6-dione
Cavia porcellus
-
-
0.00000034 - 0.1129
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
0.000001
2-[[4-[4-pyridin-4-yl-1-(2,2, 2-trifluoroethyl)pyrazol-3-yl]phenoxy]methyl]quinoline succinic acid
Rattus norvegicus
-
the IC50 of the compound for inhibition of PDE10A in vitro is less than 1 nM
-
0.00000032 - 0.0523
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
0.0152
8-methoxymethyl-isobutylmethylxanthine
Bos taurus
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.00061
erythro-9-(2-hydroxy-3-nonyl)adenine
Homo sapiens
-
IC50: 0.00061 mM for wild-type enzyme
0.0032
nimodipine
Bos taurus
-
isoform PDE1, pH and temperature not specified in the publication
0.01
additional information
Homo sapiens
-
IC50 for vardenafil, sildenafil and tadalafil is above 10000 nM, PDE2
-
0.0001
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.0001 mM, PDE3A
0.00028
(-)-6-(3-(3-cyclopropyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.00028 mM, PDE3B
0.000006
(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
Homo sapiens
-
IC50: 0.000006 mM, PDE3
0.0012
(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
Homo sapiens
-
IC50: 0.0012 mM, PDE2
0.015
(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
Homo sapiens
-
IC50: 0.015 mM, PDE1
0.00000034
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.00000034 mM, PDE3A, highly selective PDE3 inhibitor
0.0000019
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.0000019 mM, PDE3B
0.0209
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.0.0209 mM, PDE2
0.1129
2-cyclohexyl-2-methyl-N1-[3-(2-oxo-1,2-dihydro-6-quinolyl,oxy)propyl]-1-hydrazinecarboxamide
Bos taurus
-
IC50: 0.1129 mM, PDE1
0.02654
3-isobutyl-1-methyl-1H-purine-2,6(3H,7H)-dione
Homo sapiens
-
IC50: 0.02654 mM, PDE4A4
0.00000032
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.00000032 mM, PDE3A, highly selective PDE3 inhibitor
0.0000015
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.0000015 mM, PDE3B
0.0429
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.0429 mM, PDE1
0.0523
6-(3-(3-cyclooctyl-3-((1R,2R)-2-hydroxycyclohexyl)ureido)-propoxy)-2(1H)-quinolinone
Bos taurus
-
IC50: 0.0523 mM, PDE2
0.00144
dioclein
Bos taurus
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
0.00247
dioclein
Bos taurus
-
isoform PDE1 in calmodulin-activated state, pH and temperature not specified in the publication
0.0382
dioclein
Homo sapiens
-
isoform PDE2 in calmodulin-activated state, pH and temperature not specified in the publication
0.1
dioclein
Homo sapiens
-
isoform PDE2 in basal-activated state, pH and temperature not specified in the publication
0.0038
sildenafil
Homo sapiens
-
IC50: 3800 nM, 1000fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.000073
tadalafil
Homo sapiens
-
IC50: 73 nM, 40fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.00084
vardenafil
Homo sapiens
-
IC50: 840 nM, 9300fold selectivity for PDE5A1 compared to PDE11A4. This drug (PDE5 inhibitor in treatment of erectile dysfunction) is very unlikely to crossreact with PDE11A4 in patients taking the prescribed dosage of this medication
0.185
vinpocetine
Bos taurus
-
isoform PDE1 in basal-activated state, pH and temperature not specified in the publication
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SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
assay procedure of calmodulin-dependent cyclic nucleotide phosphodiesterase
additional information
-
description of a technique used to estimate the extent of PDE1 activation in vivo by measuring in vitro the PDE activity
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pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
5 - 9
-
PdeB shows no 3',5'-cAMP phosphodiesterase activity at or below pH 6
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TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
40
-
the optimum temperature for the 3',5'-cAMP phosphodiesterase activity of PdeA is 40°C
50
50
-
the optimum temperature for the 3',5'-cAMP phosphodiesterase activity of PdeA is 50°C
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TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
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ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
-
-
brenda