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Information on EC 3.1.4.1 - phosphodiesterase I and Organism(s) Rattus norvegicus and UniProt Accession Q924C3
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3.1.4.1 phosphodiesterase IIUBMB Comments
Hydrolyses both ribonucleotides and deoxyribonucleotides. Has low activity towards polynucleotides. A 3'-phosphate terminus on the substrate inhibits hydrolysis.
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Word Map
- 3.1.4.1
- camp
- phosphodiesterases
- calcification
- arterial
-
topoisomerase
- rolipram
- monophosphate
-
camp-specific
-
infancy
- osteoblast
-
hypophosphatemic
- rickets
- camptothecin
-
pseudoxanthoma
-
ectoenzyme
- topotecan
-
5'-nucleotide
- elasticum
- ibmx
- ankylosis
- 3'-phosphate
- zaprinast
-
top1-dna
- camp-pde
-
tcf7l2
- milrinone
-
tissue-nonspecific
-
cgmp-inhibited
-
cgmp-stimulated
-
pyrophosphohydrolase
- cilomilast
-
cementum
- 3-isobutyl-1-methylxanthine
-
rolipram-sensitive
- vinpocetine
-
cardiotonic
- pharmacology
- medicine
- synthesis
- drug development
- biotechnology
- analysis
The taxonomic range for the selected organisms is: Rattus norvegicus
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Synonyms
enpp1, pde4a, phosphodiesterase i, pde i, tyrosyl-dna phosphodiesterase 1, ectonucleotide pyrophosphatase/phosphodiesterase 1, nucleotide phosphodiesterase, cpsf-73, 5'-phosphodiesterase, ectonucleotide pyrophosphatase phosphodiesterase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
5'-exonuclease
-
-
-
-
5'-nucleotide phosphodiesterase
-
-
-
-
5'-phosphodiesterase
-
-
-
-
nucleotide pyrophosphatase/phosphodiesterase I
orthophosphoric diester phosphohydrolase
-
-
-
-
PC-1
nucleotide pyrophosphatase/phosphodiesterase I
-
membrane alkaline phosphodiesterase is the same enzyme as nucleotide pyrophosphatase
PC-1
-
PC-1, plasma-cell differentiation antigen-1, a trifunctional enzyme, displaying a phosphodiesterase I /nucleotide pyrophosphatase activity, a protein threonine kinase activity, and a nucleotide-stimulated protein threonine phosphatase activity
PC-1
-
PC-1, plasma-cell differentiation antigen-1, membrane glycoprotein, has 5'-nucleotide phosphodiesterase and nucleotide pyrophosphatase activity
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
PC-1, enzymic activities and regulation of PC-1
-
hydrolytically removes 5'-nucleotides successively from the 3'-hydroxy termini of 3'-hydroxy-terminated oligonucleotides
catalytic mechanism, the enzyme has a unique catalytic cycle, structure-function analysis overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
phosphoric ester hydrolysis
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
oligonucleotide 5'-nucleotidohydrolase
Hydrolyses both ribonucleotides and deoxyribonucleotides. Has low activity towards polynucleotides. A 3'-phosphate terminus on the substrate inhibits hydrolysis.
CAS REGISTRY NUMBER
COMMENTARY
9025-82-5
-
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
4-nitrophenyl uridine 5'-phosphate + H2O
4-nitrophenol + uridine 5'-phosphate
-
-
-
-
?
5'-p-nitrophenyl deoxythymidine 5'-phosphate + H2O
5'-dTMP + p-nitrophenol
-
nucleotide pyrophosphatase/phosphodiesterase I
-
-
?
5'-p-nitrophenylnucleoside 5'-monophosphate + H2O
nucleoside 5'-monophosphate + p-nitrophenol
-
-
-
?
5'-p-nitrophenyluridine 5'-phosphate + H2O
5'-UMP + p-nitrophenol
-
-
-
-
?
diethenoadenosine polyphosphate + H2O
ethenoadenosine 5'-monophosphate + ethenoadenosine (n-1)5'-polyphosphate
-
-
-
-
?
p-nitrophenyl 5'-thymidine monophosphate + H2O
p-nitrophenol + 5'-thymidine monophosphate
-
-
-
-
?
thymidine 5'-monophosphate p-nitrophenylester + H2O
p-nitrophenol + TMP
-
-
-
?
DNA + H2O
DNA(n-1) + 2'-deoxynucleoside 5'-phosphate
-
heat-denatured: very slowly, native DNA is not hydrolyzed
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
-
-
-
-
?
oligonucleotides + H2O
oligonucleotides(n-1) + 5'-mononucleotides
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
-
-
-
-
?
p-nitrophenylthymidine 5'-phosphate + H2O
5'-TMP + p-nitrophenol
-
PC-1
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
-
very slowly
-
-
?
polynucleotides + H2O
polynucleotides(n-1) + 5'-mononucleotides
-
specific for 3'-5'-direction from the 3'-hydroxyl terminal in a stepwise manner
-
-
?
additional information
?
-
-
no activity with dinucleotides bearing 3'-phosphate
-
-
?
additional information
?
-
-
enzyme does not have a strict base specificity, it does not attack oligonucleotides with a 3'-phosphate terminal
-
-
?
additional information
?
-
-
no activity with p-nitrophenylthymidine 3'-phosphate
-
-
?
additional information
?
-
-
phosphodiesterase activity results in the cleavage of nucleotides from nucleic acids and thus may be involved in catabolism of extracellular DNA. Essential function may be to hydrolyze polyribo- and polydeoxyribonucleotides. The enzyme may be important in cell differentiation during carcinogenesis
-
-
?
additional information
?
-
-
PC-1, plasma-membrane-associated enzyme with nucleotide pyrophosphatase/phosphodiesterase I activity is probably involved in the clearance of extracellular nucleotides such as ATP and diadenosine polyphosphates
-
-
?
additional information
?
-
-
isoform NPP1 is involved in cleavage of extracellular diadenosine polyphosphates in brain
-
-
?
additional information
?
-
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
?
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
additional information
?
-
-
phosphodiesterase activity results in the cleavage of nucleotides from nucleic acids and thus may be involved in catabolism of extracellular DNA. Essential function may be to hydrolyze polyribo- and polydeoxyribonucleotides. The enzyme may be important in cell differentiation during carcinogenesis
-
-
?
additional information
?
-
-
PC-1, plasma-membrane-associated enzyme with nucleotide pyrophosphatase/phosphodiesterase I activity is probably involved in the clearance of extracellular nucleotides such as ATP and diadenosine polyphosphates
-
-
?
additional information
?
-
-
isoform NPP1 is involved in cleavage of extracellular diadenosine polyphosphates in brain
-
-
?
additional information
?
-
substrates are protein-DNA adducts, such as camptothecin stabilized Topo1-DNA adducts, and modified nucleotides, including oxidized nucleotides and chain terminating nucleoside analogues
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
divalent cations
Mg2+
Zn2+
Ca2+
-
or Mg2+, basal level required, no significant increase in activity by addition of 0.1 mM Ca2+ or Mg2+
Mg2+
-
or Ca2+, basal level required, no significant increase in activity by addition of 0.1 mM Ca2+ or Mg2+
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10,12-dibromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1,3-bis(4-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-chlorophenyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(4-methylphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-1-(furan-2-ylmethyl)-3-(4-methylphenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
10-bromo-3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
11,13-dibromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
11-bromo-1,2,3,4-tetrahydro-9H-[1]benzothieno[2',3':4,5]pyrimido[6,1-b]quinazolin-9-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
3-(4-chlorophenyl)-1-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
3-(4-methoxy-phenyl)-1-(3-nitro-phenyl)-8Hpyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
3-(4-methoxyphenyl)-1-(3-nitrophenyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(2-furyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-chlorophenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9,11-dibromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9,11-dibromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1,2-dimethyl-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-chlorophenyl)-3-(4-tolyl)-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
-
-
9-bromo-1-(4-chlorophenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-methoxyphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
9-bromo-1-(4-methylphenyl)-7H-thieno[2',3':4,5]pyrimido[6,1-b]quinazolin-7-one
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
IBMX
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intra peritoneal to the rats
IC86340
-
a PDE1 inhibitor, significantly reduces collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture, and acts synergistically with bicarbonate, in the absence of bicarbonate of IC86340, itself has no effect on collagen I protein. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Lysosome inhibitors,. i.e. 2',4'-dichlorobenzamil, a nonselective CNG channel blocker, and the more specific CNG channel blocker, L-cisdiltiazem, block IC86340-mediated collagen I reduction, overview
-
indomethacin
-
PDE1 inhibitor for anti-inflammatory activity assays, the compound is suspended in 0.5% aqueous carboxy methyl cellulose solution and administered orally as well as intraperitoneal to the rats
EDTA
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: glycine-enhanced inhibition, reversed by Mg2+
EDTA
-
complete inhibition, addition of EDTA plus Ca2+ or Mn2+ results in partial inhibition
glycine
-
liver, 0.1 M glycine, inhibition initially 20-30%, 90% inhibition obtained after 60 min preincubation
glycine
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: at high concentrations, 100 mM
glycine
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: glycine-enhanced inhibition by EDTA, by itself, up to 25 mM, is not inhibitory
additional information
-
not inhibitory to renal ecto-phosphodiesterase: 8-methoxymethyl-3-isobutyl-1-methylxanthine, erythro-9-(2-hydroxy-3-nonyl)adenine, milrinone, cGMP, 4-(3-butoxy-4-methoxybenzyl)imidazolidin-2-one, zaprinast, 5-nitro-2,N,N-trimethylbenzenesulfonamide
-
additional information
-
not inhibitory: levamisole, sodium azide, gadolinium chloride
-
additional information
-
not inhibitory: ouabain, N-ethylmaleimide, levamisole, sodium azide
-
additional information
-
synthesis of 1,2,9,11-tetrasubstituted 7H-thieno[2',3':4,5]pyrimido[6,1-b]-quinazolin-7-one and 1,3,10,12-tetrasubstituted 8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one inhibitors, synthesis and evaluation, overview
-
additional information
-
bicarbonate acts synergistically with inhibitor IC86340
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
dexamethasone
-
increases alkaline phosphodiesterase I in a dose- and time-dependent manner, maximal increase after treatment with 0.001 mM dexamethasone for 5 days, stimulation by dexamethasone is suppressed by cycloheximide and RU 38486
additional information
etoposide and doxorubicin trigger a series of events that eventually lead to an enhanced DNA-linkage of topo I, which then is acted upon by the enzyme TDP1
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.097
thymidine 5'-monophosphate p-nitrophenylester
-
pH 9.6, gp115, AS30D protein
0.22
thymidine 5'-monophosphate p-nitrophenylester
-
pH 9.6, gp120/gp110, liver protein
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0399
3-(4-methoxy-phenyl)-1-(3-nitro-phenyl)-8Hpyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
Rattus norvegicus
-
-
0.337
9,11-dibromo-1-(4-methoxyphenyl)-3-phenyl-8H-pyrido[2',3':4,5]pyrimido[6,1-b]quinazolin-8-one
Rattus norvegicus
-
-
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
411
-
PC-1, phosphodiesterase I activity, substrate: p-nitrophenylthymidine 5'-phosphate
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
9 - 9.1
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
-
arteries from hypertensive rats, vascular PDE1A, PDE1B, PDE1C, and PDE5 isoforms
-
colocalization with ecto-nucleoside triphosphate diphosphohydrolase and ecto-5'-nuleotidase on platelet surface
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
-
highest enzyme activities in synaptic membranes from cerebellum, hypothalamus, hippocampus
-
primary cell culture of submandibular salivary gland, co-localization of enzyme with an ecto-ATP diphosphohydrolase and an ecto-5'-nucleotidase
-
heart left ventricle, expression of isoforms NPP2 and NPP3, not NPP1. NPP3 shows the highest abundance
-
ecto-phosphodiesterase activity is not mediated by isoform PDE1, PDE2, PDE3, PDE4, PDE5, PDE6, PDE7, PDE9, PDE10,or PDE11 activity
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
PC-1, active site of plasma-membrane-associated PC-1 appears to be located extracellularly
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
(R,S)-isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1, an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression, overview
evolution
the enzyme belongs to the phospholipase D, PLD, superfamily, which consists of a highly diverse collection of prokaryotic and eukaryotic enzymes, such as bacterial, plant and mammalian PLDs, cardiolipin and phosphatidylserine synthases, Salmonella typhimurium Nuc and mammalian DNase II endonucleases, restriction enzyme BfiI, poxvirus envelope proteins p37K and K4L, and eukaryotic Tdp1, sequence comparison. Family members show the presence of two histidine-lysine-aspartate-asparagine-HKDN-(HxKx4Dx6N; x being any amino acid) motifs
malfunction
-
phosphodiesterase-1 inhibition decreases vascular contraction in arteries from angiotensin II hypertensive, but not control, rats
physiological function
physiological function
-
phosphodiesterase 1 plays a role in decreased cGMP level contributing to increased contraction in arteries from hypertensive rats. Ang II augments PDE1 activation, decreasing the bioavailability of cyclic guanosine 3',5'-monophosphate, and contributing to increased vascular contractility, effects of different PDF isozymes, overview
physiological function
-
role and underlying mechanism of cyclic nucleotide phosphodiesterase 1, PDE1, in regulating collagen I in synthetic vascular smooth muscle cells, overview
physiological function
tyrosyl-DNA phosphodiesterase I is a eukaryotic DNA repair enzyme that catalyzes the removal of covalent 3'-DNA adducts, the enzyme hydrolyzes the 3'-phospho-tyrosyl that in the cell covalently links DNA topoisomerase I and DNA
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). ENPP1_RAT
906
1
102942
Swiss-Prot
other Location (Reliability: 2)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
PC-1, nucleotide pyrophosphatase/phosphodiesterase I: EDTA favors thermal inactivation, divalent cations protect from thermal inactivation
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
PC-1, nucleotide pyrophosphatase/phosphodiesterase I, divalent cations protect from thermal inactivation
-
ORGANIC SOLVENT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Acetone
-
phosphodiesterase I is destroyed during preparation of an acetone powder
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
nucleotide pyrophosphatase/phosphodiesterase I, -20øC, 1 mg/ml bovine serum albumin, stable for at least 1 year
-
nucleotide pyrophosphatase/phosphodiesterase I, once thawed, 4øC, 1 mg/ml bovine serum albumin, stable for at least 1 month
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
cAMP-dependent inhibition of NPP1 expression not involving the the activator protein-1 motif present in the promoter of the rat NPP1 gene. (R,S)-Isoproterenol decreases the amount of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 protein by 75% and 81%, respectively. Contrary to downregulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 , an upregulation of glial fibrillary acidic protein, a differentiation marker for astrocytic cells is observed. Ca2+, PKA, PI 3-K/PKB/GSK-3, Epac/Rap1/PP2A and MAP kinase modules are not involved in the inhibition of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 gene expression
RENATURED/Commentary
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pharmacology
-
phosphodiesterase plays an important role in regulating cAMP and cGMP, und thus becomes an important site for the pharmacological intervention, i.e. Parkinson's disease, inhibition studies with theinopyrimidine fused quinazolines and pyridopyrimidine fused quinazolinones
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Futai, M.; Mizuno, D.
A new phosphodiesterase forming nucleoside 5'-monophosphate from rat liver. Its partial purification and substrate specificity for nicotinamide adenine dinucleotide and oligonucleotides
J. Biol. Chem.
242
5301-5307
1967
Rattus norvegicus
Razzell, W.E.
Tissue and intracellular distribution of two phophodiesterases
J. Biol. Chem.
236
3028-3030
1961
Homo sapiens, Rattus norvegicus, Sus scrofa
Lopez-Gomez, J.; Costas, M.J.; Meireles Ribeiro, J.; Fernandez, A.; Romero, A.; Avalos, M.; Cameselle, J.C.
Glycine-enhanced inhibition of rat liver nucleotide pyrophosphatase/phosphodiesterase-I by EDTA: a full account of the reported inhibition by commercial preparations of acidic fibroblast growth factor (FGF-1)
FEBS Lett.
421
77-79
1998
Rattus norvegicus
Uriarte, M.; Stalmans, W.; Hickman, S.; Bollen, M.
Regulation of purified hepatic PC-1 (phosphodiesterase-I/nucleotide pyrophosphatase) by threonine auto(de)phosphorylation and by binding of acidic fibroblast growth factor
Biochem. J.
306
271-277
1995
Rattus norvegicus
Stefanovic, V.; Vlahovic, P.; Ardaillou, R.
Characterization and control of expression of cell surface alkaline phosphodiesterase I activity in rat mesangial glomerular cells
Renal Physiol. Biochem.
18
12-20
1995
Rattus norvegicus
Yano, T.; Funakoshi, I.; Yamashina, I.
Purification and properties of nucleotide pyrophosphatase from human placenta
J. Biochem.
98
1097-1107
1985
Rattus norvegicus
Cameselle, J.C.; Costas, M.J.; Sillero, M.A.G.; Sillero, A.
Two low Km hydrolytic activities on dinucleoside 5',5'''-P1,P4-tetraphosphates in rat liver. Characterization as the specific dinucleoside tetraphosphatase and a phosphodiesterase-I-like enzyme
J. Biol. Chem.
259
2879-2885
1984
Rattus norvegicus
Garcia-Nieto, R.M.; Jose, E.S.; Martin-Nieto, J.; Villalobo, A.
Characterization of a new plasma membrane-associated ecto-5'-phosphodiesterase/nucleotide-pyrophosphatase from rat hepatocarcinoma AS-30D cells
J. Physiol. Biochem.
57
31-40
2001
Rattus norvegicus
Fuerstenau, C.R.; Trentin, D.d.S.; Barreto-Chaves, M.L.; Sarkis, J.J.
Ecto-nucleotide pyrophosphatase/phosphodiesterase as part of a multiple system for nucleotide hydrolysis by platelets from rats: kinetic characterization and biochemical properties
Platelets
17
84-91
2006
Rattus norvegicus
Henz, S.L.; Fuerstenau, C.R.; Chiarelli, R.A.; Sarkis, J.J.
Kinetic and biochemical characterization of an ecto-nucleotide pyrophosphatase/phosphodiesterase (EC 3.1.4.1) in cells cultured from submandibular salivary glands of rats
Arch. Oral Biol.
52
916-923
2007
Rattus norvegicus
Jackson, E.K.; Ren, J.; Zacharia, L.C.; Mi, Z.
Characterization of renal ecto-phosphodiesterase
J. Pharmacol. Exp. Ther.
321
810-815
2007
Rattus norvegicus
Ruecker, B.; Almeida, M.E.; Libermann, T.A.; Zerbini, L.F.; Wink, M.R.; Sarkis, J.J.
Biochemical characterization of ecto-nucleotide pyrophosphatase/phosphodiesterase (E-NPP, E.C. 3.1.4.1) from rat heart left ventricle
Mol. Cell. Biochem.
306
247-254
2007
Rattus norvegicus
Asensio, A.C.; Rodriguez-Ferrer, C.R.; Castaneyra-Perdomo, A.; Oaknin, S.; Rotllan, P.
Biochemical analysis of ecto-nucleotide pyrophosphatase phosphodiesterase activity in brain membranes indicates involvement of NPP1 isoenzyme in extracellular hydrolysis of diadenosine polyphosphates in central nervous system
Neurochem. Int.
50
581-590
2007
Rattus norvegicus
Laddha, S.S.; Bhatnagar, S.P.
A new therapeutic approach in Parkinsons disease: some novel quinazoline derivatives as dual selective phosphodiesterase 1 inhibitors and anti-inflammatory agents
Bioorg. Med. Chem.
17
6796-6802
2009
Bos taurus, Rattus norvegicus
Cai, Y.; Miller, C.L.; Nagel, D.J.; Jeon, K.I.; Lim, S.; Gao, P.; Knight, P.A.; Yan, C.
Cyclic nucleotide phosphodiesterase 1 regulates lysosome-dependent type I collagen protein degradation in vascular smooth muscle cells
Arterioscler. Thromb. Vasc. Biol.
31
616-623
2011
Rattus norvegicus
Aerts, I.; Grobben, B.; Van Ostade, X.; Slegers, H.
Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma
Eur. J. Pharmacol.
654
1-9
2011
Rattus norvegicus (Q924C3), Rattus norvegicus Wistar (Q924C3)
Giachini, F.R.; Lima, V.V.; Carneiro, F.S.; Tostes, R.C.; Webb, R.C.
Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats: role of phosphodiesterase 1
Hypertension
57
655-663
2011
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
Comeaux, E.Q.; van Waardenburg, R.C.
Tyrosyl-DNA phosphodiesterase I resolves both naturally and chemically induced DNA adducts and its potential as a therapeutic target
Drug Metab. Rev.
46
494-507
2014
Canis lupus familiaris (E2REL5), Gallus gallus (F1NSQ5), Saccharomyces cerevisiae (P38319), Rattus norvegicus (Q4G056), Mus musculus (Q8BJ37), Homo sapiens (Q9NUW8), Drosophila melanogaster (Q9VQM4), Saccharomyces cerevisiae ATCC 204508 (P38319)
EXTERNAL LINKS (specific for EC-Number 3.1.4.1)
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