Information on EC 3.1.4.35 - 3',5'-cyclic-GMP phosphodiesterase and Organism(s) Homo sapiens

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


The taxonomic range for the selected organisms is: Homo sapiens

EC NUMBER
COMMENTARY hide
3.1.4.35
-
RECOMMENDED NAME
GeneOntology No.
3',5'-cyclic-GMP phosphodiesterase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
hydrolysis of phosphoric ester
-
-
-
-
PATHWAY
BRENDA Link
KEGG Link
MetaCyc Link
Purine metabolism
-
-
SYSTEMATIC NAME
IUBMB Comments
3',5'-cyclic-GMP 5'-nucleotidohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9068-52-4
-
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
inhibition of PDE-5 slows cGMP degradation, leading to increased levels of cGMP and greater blood flow through the corpus cavernosum when nitric oxide is released during sexual stimulation, PDE-5 inhibitors have little effect on corpus cavernosum blood flow
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2'-O-anthraniloyl-cGMP + H2O
?
show the reaction diagram
-
phosphorylation increases affinity for hydrolysis of 2'-O-anthraniloyl-cGMP by about 3fold
-
-
?
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
phosphodiesterase 5 converts the second messenger 3',5'-cGMP to its inactive form
-
-
?
cGMP + H2O
5'-GMP
show the reaction diagram
-
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
additional information
?
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
3',5'-cGMP + H2O
5'-GMP
show the reaction diagram
3',5'-cGMP + H2O
guanosine 5'-phosphate
show the reaction diagram
-
phosphodiesterase 5 converts the second messenger 3',5'-cGMP to its inactive form
-
-
?
guanosine 3',5'-cyclic phosphate + H2O
guanosine 5'-phosphate
show the reaction diagram
additional information
?
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Ca2+
slight activation of PDE9A1
Mn2+
required for activity, maximal activity at approx. 10 mM
Zn2+
-
approx. 2.5 fold activation at 0.01 mM, strong inhibition above
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(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: 0.00067 mM, PDE5
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
-
filaminast
1,2-dihydro-2-[(2-methyl-4-pyridinyl)methyl]-1-oxo-8-(2-pyrimidinylmethoxy)-4-(3,4,5-trimethoxyphenyl)-2,7-naphthyridine-3-carboxylic acid methyl ester hydrochloride
-
specific inhibitor of PDE5
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
-
-
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
i.e. BAY 73-6691, IC50: 55 nM
1-(2-ethoxyethyl)-3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
1-(2-ethoxyethyl)-3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
1-(3-chloro-4-methoxybenzyl)-3-(cis-4-hydroxycyclohexyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-carbonitrile
-
-
1-[4-[(1,3-benzodioxol-5-ylmethyl)amino]-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid
-
-
1-[9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl]piperidin-4-ol
-
-
1-[9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-6-yl]piperidine-4-carboxylic acid
-
-
1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate
-
trivial name sildenafil citrate or Viagra
2,2',2'',2'''-[(4,8-dipiperidin-1-ylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
-
-
2-(2,4-dihydroxyphenyl)-8-[5-hydroxy-5-methyl-2-(1-methylethenyl)hexyl]-5-methoxy-4H-chromene-3,7-diol
-
-
2-(2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
-
2-(2-propoxyphenyl)-1,7-dihydro-6H-purin-6-one
-
-
2-(5-amino-2-propoxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-one
-
-
2-(5-[[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl]-2-propoxyphenyl)-5-methylquinazolin-4(3H)-one
-
-
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
-
2-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
-
-
2-[2-ethoxy-5-(4-ethyl-piperazine-1-sulfonyl)phenyl]-5-methyl-7-propyl-3H-imidazo[5,1-f][1,2,4]triazin-4-one
-
trivial name vardenafil or Levitra
2-[2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
-
vardenafil
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
-
-
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
-
piclamilast
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
-
roflumilast
3-ethyl-5-(4-methyl-1,4-diazepan-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(morpholin-4-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-1-(2-propoxyethyl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-1-[2-(propan-2-yloxy)ethyl]-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-(piperazin-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(4-fluorophenyl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-ethyl-N5-(1-methylpiperidin-4-yl)-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
-
3-isobutyl-1-methylxanthine
3-methyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-5-[(3S)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-methyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
3-[(6-deoxy-alpha-L-mannopyranosyl)oxy]-5-hydroxy-8-(1-hydroxy-2-methylprop-2-en-1-yl)-2-(4-methoxyphenyl)-4-oxo-3,4-dihydro-2H-chromen-7-yl beta-D-glucopyranoside
-
-
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
-
-
4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid
-
cilomilast
4-[3-ethyl-7-(pyrimidin-4-ylamino)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-2-one
-
-
4-[7-hydroxy-8-[5-hydroxy-5-methyl-2-(1-methylethenyl)hexyl]-5-methoxy-4H-chromen-2-yl]benzene-1,3-diol
-
-
5-(1,4-diazepan-1-yl)-3-ethyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
5-(1,4-diazepan-1-yl)-3-methyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
-
-
5-(2-propoxyphenyl)-3,6-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
-
zardaverine
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
-
-
6-benzo[1,3]dioxol-5-yl-2-methyl-2,3,6,7,12,12a-hexahydropyrazinol[1',2':1,6]pyrido[3,4-b]indole-1,4-dione
-
trivial name tadalafil or Cialis
6-deoxy-3-O-[6-deoxy-4-O-[7-(beta-D-glucopyranosyloxy)-5-hydroxy-2-(3-hydroxy-4-methoxyphenyl)-8-(2-methylprop-1-en-1-yl)-4-oxo-3,4-dihydro-2H-chromen-3-yl]-alpha-L-mannopyranosyl]-alpha-L-mannopyranose
-
-
8-(5-[[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]sulfonyl]-2-propoxyphenyl)-6-propyl-6,6a,9,9a-tetrahydro-5H-[1,2,4]triazolo[3,4-i]purin-5-one
-
-
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
-
-
9-[(3-chloro-4-methoxybenzyl)amino]-3-ethyl-N-methyl-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazine-6-carboxamide
-
-
amentoflavone
-
IC50: 0.0117 mM
avanafil
-
TA-1790, highly selective inhibitor of PDE5
BAY 73-6691
-
specific PDE9A inhibitor
benzamidenafil
-
i.e. N-(3,4-dimethoxy benzyl)-2-[[(1R,S)-2-hydroxy-1-methylethyl]amino]-5-nitrobenzamide, potent and specific inhibitor of PDE-5
bilobetin
-
IC50: 0.00152 mM
chamomile
-
weak, but still statistically significant inhibition of PDE5A1
Cilostamide
cone Pgamma subunit
-
PDE6C is potently inhibited by the recombinant cone and rod Pgamma-subunits with slight selectivity for the cone Pgamma
-
CP461
-
-
delphinidin
-
-
delphinidin 3-glucoside
-
-
dipyridamole
EDTA
0.5 mM, 35% inhibition of activity in the absence of a divalent metal ion
Evo48
-
potent inhibitor of PDE5
-
exisulind
-
-
ginkgetin
-
IC50: 0.00059 mM
malvidin
-
IC50: 0.0354 mM
malvidin-3-O-beta-glucoside
-
IC50: 0.0116 mM
N-(3-chloro-4-methoxybenzyl)-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine
-
-
N-(3-chloro-4-methoxybenzyl)-3-ethyl-6-(pyridin-4-ylmethyl)-3H-pyrazolo[4',3':5,6]pyrido[3,4-d]pyridazin-9-amine
-
-
N-[3-(1,3-dimethyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-propoxyphenyl]methanesulfonamide
-
-
N-[3-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]piperidine-1-carboxamide
-
-
N-[3-(4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]morpholine-4-carboxamide
-
-
N5-(2-aminoethyl)-3-ethyl-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
-
-
peonidin
-
-
peonidin 3-glucoside
-
-
petunidin
-
-
petunidin 3-glucoside
-
-
quinazolinamine
-
IC50: 0.000021 mM, PDE5
rod Pgamma subunit
-
PDE6C is potently inhibited by the recombinant cone and rod Pgamma-subunits with slight selectivity for the cone Pgamma
-
RP-73401
-
IC50: 0.0089 mM, PDE5
SCH 51866
0.0029 mM, 50% inhibition of PDE9A5, 0.0033 mM, 50% inhibition of PDE9A1
sciadopitysin
-
IC50: 0.00324 mM
sequoiaflavone
-
IC50: 0.0199 mM
sildenafil
sildenafil citrate
inhibition of PDE5 activity in the intestine, which might occur during sildenafil citrate ingestion, could result in a transitory diarrhoe
SLx-2101
-
inhibits excellent potency both ex vivo and in vivo
tadalafil
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
-
-
udenafil
UK-369,003
-
i.e. 1-[6-ethoxy-5-[3-ethyl-6,7-dihydro-2-(2-methoxyethyl)-7-oxo-2H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-pyridyl sulfonyl]-4-ethylpiperazine benzenesulfonate, a potent selective inhibitor of cGMP-specific PDE5 with more than 80fold selectivity for PDE5 over PDE6, more than 3000fold selectivity over PDEs 1-4 and 10, and more than 10000fold selectivity over PDE11
vardenafil
zaprinast
Zn2+
-
strong inhibition above 0.01 mM, almost complete inhibition at 0.1 mM
additional information
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
stable toxin
possibly due to an increase in cGMP resulting from stable toxin treatment
-
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0247 - 0.0651
2'-O-anthraniloyl-cGMP
0.065
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
0.00025 - 0.182
cGMP
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
4400
3',5'-cGMP
-
recombinant human cone PDE6C, pH and temperature not specified in the publication
0.00083 - 3.8
cGMP
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.000045
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
-
-
0.000176 - 0.0006608
2-bromo-5-ethyl-7,8-dihydro-1-[(4-hydroxyphenyl)methyl]-7(R)-(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
0.0000487 - 0.0007215
3,7-dihydro-8-[(1-hydroxymethyl)-3-cyclopenten-1-yl]amino-7-[(4-methoxyphenyl)methyl]-1,3-dimethyl-1H-purine-2,6-dione
0.01212 - 0.09485
3-isobutyl-1-methylxanthine
0.0000173 - 0.001605
5-ethyl-7,8-dihydro-2,7(R)-bis(phenylmethyl)-1H-imidazo[2,1-b]purin-4(5H)-one
0.0000026 - 0.0000183
8-bromo-1-ethyl-3,7-dihydro-7-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-1H-purine-2,6-dione
0.078 - 0.14
cone Pgamma subunit
-
0.0000035 - 0.0001735
E4021
0.105 - 0.155
rod Pgamma subunit
-
0.000013 - 0.0000984
sildenafil
0.0001778 - 0.01438
zaprinast
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00067
(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: 0.00067 mM, PDE5
0.053
(E)-1-(3-(cyclopentyloxy)-4-methoxyphenyl)ethanone O-carbamoyl oxime
Homo sapiens;
-
-
0.019
1,2-dimethoxy-12-methyl[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium
Homo sapiens;
-
-
0.000055
1-(2-chlorophenyl)-6-((2R)-3,3,3-trifluoro-2-methylpropyl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidine-4-one
Homo sapiens;
-
i.e. BAY 73-6691, IC50: 55 nM
0.0000004
1-(2-ethoxyethyl)-3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00001
1-(3-chloro-4-methoxybenzyl)-3-(cis-4-hydroxycyclohexyl)-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-6-carbonitrile
Homo sapiens;
-
-
0.0000037
1-[4-[(1,3-benzodioxol-5-ylmethyl)amino]-6-chloroquinazolin-2-yl]piperidine-4-carboxylic acid
Homo sapiens;
-
-
0.00069
2,2',2'',2'''-[(4,8-dipiperidin-1-ylpyrimido[5,4-d]pyrimidine-2,6-diyl)dinitrilo]tetraethanol
Homo sapiens;
-
-
0.000005
2-(2-ethoxyphenyl)-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
Homo sapiens;
-
-
0.00001
2-(2-propoxyphenyl)-1,7-dihydro-6H-purin-6-one
Homo sapiens;
-
-
0.0000017
2-(5-amino-2-propoxyphenyl)thieno[2,3-d]pyrimidin-4(3H)-one
Homo sapiens;
-
-
0.0000065
2-(5-[[4-(2-hydroxyethyl)piperazin-1-yl]sulfonyl]-2-propoxyphenyl)-5-methylquinazolin-4(3H)-one
Homo sapiens;
-
-
0.00001
2-methoxy-7-methyl-9-propylimidazo[1,5-a]pyrido[3,2-e]pyrazin-6(5H)-one
Homo sapiens;
-
-
0.0000007
2-[2-ethoxy-5-[(4-ethylpiperazin-1-yl)sulfonyl]phenyl]-5-methyl-7-propylimidazo[5,1-f][1,2,4]triazin-4(3H)-one
Homo sapiens;
-
-
0.0035
3-(cyclopentylmethoxy)-N-(2,6-dichlorophenyl)-4-methoxybenzamide
Homo sapiens;
-
-
0.017
3-(cyclopropylmethoxy)-N-(2,6-dichlorophenyl)-4-(difluoromethoxy)benzamide
Homo sapiens;
-
-
0.00000648
3-ethyl-5-(4-methyl-1,4-diazepan-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000392
3-ethyl-5-(morpholin-4-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.0000003
3-ethyl-5-(piperazin-1-yl)-1-(2-propoxyethyl)-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000086
3-ethyl-5-(piperazin-1-yl)-1-[2-(propan-2-yloxy)ethyl]-N-(pyridin-2-yl)-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000065
3-ethyl-5-(piperazin-1-yl)-N-(pyridin-2-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000015
3-ethyl-5-(piperazin-1-yl)-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000007
3-ethyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000009
3-ethyl-N-(4-fluorophenyl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000328
3-ethyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000101
3-ethyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000035
3-ethyl-N5-(1-methylpiperidin-4-yl)-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
Homo sapiens;
-
pH and temperature not specified in the publication
0.0000019 - 0.000327
3-isobutyl-1-methylxanthine
0.00000014
3-methyl-5-[(3R)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000094
3-methyl-5-[(3S)-3-methylpiperazin-1-yl]-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000184
3-methyl-N-(4-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000078
3-methyl-N-(6-methylpyridin-2-yl)-5-(piperazin-1-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.000014
4-(1,3-benzodioxol-5-ylmethoxy)-2-(1H-imidazol-1-yl)-5-phenylpyrimidine
Homo sapiens;
-
-
0.053
4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexanecarboxylic acid
Homo sapiens;
-
-
0.00000296
4-[3-ethyl-7-(pyrimidin-4-ylamino)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-5-yl]piperazin-2-one
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000315
5-(1,4-diazepan-1-yl)-3-ethyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.00000979
5-(1,4-diazepan-1-yl)-3-methyl-N-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidin-7-amine
Homo sapiens;
-
pH and temperature not specified in the publication
0.081
5-(2-propoxyphenyl)-3,6-dihydro-7H-[1,2,3]triazolo[4,5-d]pyrimidin-7-one
Homo sapiens;
-
-
0.00000034
8-(5-[[4-(2-hydroxyethyl)-1,4-diazepan-1-yl]sulfonyl]-2-propoxyphenyl)-6-propyl-6,6a,9,9a-tetrahydro-5H-[1,2,4]triazolo[3,4-i]purin-5-one
Homo sapiens;
-
-
0.0117
amentoflavone
Homo sapiens;
-
IC50: 0.0117 mM
0.0000011 - 0.00002
benzamidenafil
0.00152
bilobetin
Homo sapiens;
-
IC50: 0.00152 mM
0.0000405 - 0.006
Cilostamide
0.0000109
dipyridamole
Homo sapiens;
-
bladder homogenate, 30°C, pH 7.0
0.00059
ginkgetin
Homo sapiens;
-
IC50: 0.00059 mM
0.0354
malvidin
Homo sapiens;
-
IC50: 0.0354 mM
0.0116
malvidin-3-O-beta-glucoside
Homo sapiens;
-
IC50: 0.0116 mM
0.0000026
N-(3-chloro-4-methoxybenzyl)-2-pyridin-4-yl-5,6,7,8-tetrahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidin-4-amine
Homo sapiens;
-
-
0.000003
N-[3-(1,3-dimethyl-4-oxo-4,5-dihydro-1H-pyrazolo[3,4-d]pyrimidin-6-yl)-4-propoxyphenyl]methanesulfonamide
Homo sapiens;
-
-
0.0000035
N-[3-(4-oxo-3,4-dihydrothieno[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]piperidine-1-carboxamide
Homo sapiens;
-
-
0.000018
N-[3-(4-oxo-3,4-dihydro[1]benzofuro[3,2-d]pyrimidin-2-yl)-4-propoxyphenyl]morpholine-4-carboxamide
Homo sapiens;
-
-
0.00000952
N5-(2-aminoethyl)-3-ethyl-N7-(pyrimidin-4-yl)-1-[2-(2,2,2-trifluoroethoxy)ethyl]-1H-pyrazolo[4,3-d]pyrimidine-5,7-diamine
Homo sapiens;
-
pH and temperature not specified in the publication
0.000021
quinazolinamine
Homo sapiens;
-
IC50: 0.000021 mM, PDE5
0.0089
RP-73401
Homo sapiens;
-
IC50: 0.0089 mM, PDE5
0.00324
sciadopitysin
Homo sapiens;
-
IC50: 0.00324 mM
0.0199
sequoiaflavone
Homo sapiens;
-
IC50: 0.0199 mM
0.0000013 - 0.01
sildenafil
0.0000018 - 0.01
tadalafil
0.0000004
trans-4-([2-[(3-chloro-4-methoxyphenyl)carbamoyl]-4-cyanophenyl]carbamoyl)cyclohexanecarboxylic acid
Homo sapiens;
-
-
0.00000006 - 0.00337
vardenafil
0.0000088
zaprinast
Homo sapiens;
-
bladder homogenate, 30°C, pH 7.0
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6 - 8.5
-
almost no activity at pH 6.0 and 8.5, respectively
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
phosphodiesterase 5 is exclusively detected in smooth muscle cells of the wall, no activity in vascular endothelial layer
Manually annotated by BRENDA team
-
PDE5 is limited to the smooth muscle of the clitoral erectile tissue; presence of isoform PDE5 in smooth muscle of the clitoral erectile tissue
Manually annotated by BRENDA team
-
PDE5
Manually annotated by BRENDA team
-
colon cancer cell
Manually annotated by BRENDA team
-
muscle fibers of bladder
Manually annotated by BRENDA team
-
PFE9A gene expression is higher in neutrophils from sickle cell disease individuals compared to control cells
Manually annotated by BRENDA team
-
PFE9A gene expression is higher in reticulocytes from sickle cell disease individuals compared to control cells
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
-
low gene expression
Manually annotated by BRENDA team
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
isoform PDE5 is localized in discrete cytoplasmic foci; PDE5 is localized in discrete cytoplasmic foci
Manually annotated by BRENDA team
splice variant PDE9A5
Manually annotated by BRENDA team
splice variant PDE9A1
Manually annotated by BRENDA team
PDB
SCOP
CATH
UNIPROT
ORGANISM
Homo sapiens;
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
72000
-
PDE9, SDS-PAGE
99000
x * 99000, SDS-PAGE of recombinant His-tagged protein
105000
2 * 105000, immunoblot
125000
-
recombinant enhanced green fluorescent protein fusion protein of human cone PDE6C
200000
gel filtration
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
?
x * 99000, SDS-PAGE of recombinant His-tagged protein
dimer
2 * 105000, immunoblot
additional information
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoprotein
side-chain modification
-
PDE5 is phosphorylated at Ser102 by cyclic nucleotide-dependent protein kinases, phosphorylation activates PDE5 catalytic site independently of cGMP binding to the allosteric sites
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
crystals of PDE5A1 complexed with the inhibitors sildenafil, tadalafil or vardenafil, PDE5A1-inhibitor complex crystals are grown at 4°C by hanging-drop vapour diffusion, adding 0.001 ml protein solution containing 10 mg/ml protein in 25 mM Tris-HCl, pH 7.5, 100 mM NaCl and 5 mM dithiothreitol, to 0.001 ml well solution consisting of 100 mM Tris-HCl, pH 7.2-7.5, 200 mM MgCl2 and 6-9% polyethylene glycol 8000, crystals diffract to 2.3-2.8 A
-
hanging drop method, PDE5A1 in complex with the nonselective inhibitor 3-isobutyl-1-methylxanthine
-
molecular dynamics simulations based on crystal structure PDB code 1RKP. The second bridging ligand in the active site is HO- rather than H2O, serving as a nucleophile to initialize the catalytic hydrolysis of cGMP
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
chitin column chromatography
-
immunoprecipitation with Dynabeads with Protein G
-
Mono Q, partially purified
-
Ni-NTA agarose column chromatography
-
recombinant catalytic domain of PDE5A1
-
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
cloning of cDNA, expression of PDE5A GAF domain in Escherichia coli
-
cloning of cDNA, expression of PDE9A5 in HEK293 cells
cloning of cGMP-binding domain and expression as GST-fusion protein in Escherichia coli
-
cloning of rod PDE6 alpha and beta subunits and cone PDE6alpha', expression in Sf9 cells
-
ectopic expression of the enhanced green fluorescent protein fusion protein of human cone PDE6C in rods of transgenic Xenopus laevis
-
expressed in Escherichia coli
-
expression of his-tagged protein in baculovirus/Sf9 system
expression of isoform PDE5A1 in COS-7 cells
-
expression of PDE isoenzymes PDEA1, PDEA2 and PDEA3 in COS-7 cells
-
expression of the catalytic domain of PDE5A1 in Escherichia coli
-
fusion protein of wild-type and mutant F163A GAFa domain of enzyme to Green Fluorescent Protein or Renilla luciferase
-
splice variants PDE5A1 and PDE5A2
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D299A
-
mutation in GAF-domain, no change in cGMP binding affinity
F163A
-
mutantion in GAFa domain of enzyme, mutant is unable to bind cGMP
F205A
-
mutation in GAF-domain, no cGMP binding
F205Q
-
mutation in GAF-domain, no cGMP binding
F786A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
F820A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
H613A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
L765A
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Q817A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
V782A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612A
decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
Y612F
modest decrease in affinities for substrate cGMP and inhibitors vardenafil, sildenafil, tadalafil, 3-isobutyl-1-methylxanthine
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
analysis
-
fusion protein of wild-type and mutant F163A GAFa domain of enzyme to Green Fluorescent Protein or Renilla luciferase for use in bioluminescence resonance energy transfer assay BRET as a biosensor of cGMP. BRET ratios of wild-type, but not mutant F163A, increase in presence of cGMP, but not cAMP
medicine