Any feedback?
Please rate this page
(enzyme.php)
(0/150)

BRENDA support

BRENDA Home
show all | hide all No of entries

Information on EC 3.6.1.17 - bis(5'-nucleosyl)-tetraphosphatase (asymmetrical) and Organism(s) Lupinus angustifolius and UniProt Accession O04841

for references in articles please use BRENDA:EC3.6.1.17
Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
IUBMB Comments
Also acts on bis(5'-xanthosyl)-tetraphosphate and, more slowly, on bis(5'-adenosyl)-tetraphosphate and bis(5'-uridyl)-tetraphosphate [cf. EC 3.6.1.41 bis(5'-nucleosyl)-tetraphosphatase (symmetrical)]
Specify your search results
Select one or more organisms in this record: ?
This record set is specific for:
Lupinus angustifolius
UNIPROT: O04841
Show additional data
Do not include text mining results
Include (text mining) results
Include results (AMENDA + additional results, but less precise)
Word Map
hide
The taxonomic range for the selected organisms is: Lupinus angustifolius
The enzyme appears in selected viruses and cellular organisms
Synonyms
ap4a hydrolase, nudt2, diadenosine tetraphosphatase, enpp4, ap4aase, ndx-4, ct771, dinucleoside tetraphosphatase, ap4a-hydrolase, dipp1, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
diadenosine 5,5-P1,P4-tetraphosphate hydrolase
-
(asymmetrical) diadenosine 5',5''‚-P1,P4-tetraphosphate hydrolase
-
-
(asymmetrical) dinucleoside tetraphosphatase
-
-
Ap4A hydrolase
AP4AASE
-
-
-
-
asymmetrical Ap4A hydrolase
-
-
bis(5'-adenosyl)-tetraphosphatase
-
-
-
-
bis(5'-guanosyl)-tetraphosphatase
-
-
-
-
bis(5'-nucleosyl)-tetraphosphatase (asymmetrical)
-
-
bis(5-guanosyl)tetraphosphatase
-
-
-
-
Diadenosine 5',5'''-P1,P4-tetraphosphate asymmetrical hydrolase
-
-
-
-
diadenosine P1,P4-tetraphosphatase
-
-
-
-
Diadenosine tetraphosphatase
-
-
-
-
diguanosine tetraphosphatase
-
-
-
-
diguanosinetetraphosphatase (asymmetrical)
-
-
-
-
diguanosinetetraphosphate guanosylhydrolase
-
-
-
-
dinucleoside tetraphosphatase
-
-
-
-
dinucleosidetetraphosphatase (asymmetrical)
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphorous acid anhydride hydrolysis
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
P1,P4-bis(5'-nucleosyl)-tetraphosphate nucleotidohydrolase
Also acts on bis(5'-xanthosyl)-tetraphosphate and, more slowly, on bis(5'-adenosyl)-tetraphosphate and bis(5'-uridyl)-tetraphosphate [cf. EC 3.6.1.41 bis(5'-nucleosyl)-tetraphosphatase (symmetrical)]
CAS REGISTRY NUMBER
COMMENTARY hide
37289-29-5
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
P1,P4-bis(5'-adenosyl) tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
?
(2'-pdA)AppppA + H2O
?
show the reaction diagram
-
cleavage to produce ATP and 2'-deoxyadenylated AMP rather than 2'-deoxyadenylated ATP + AMP occurs with a ratio of 60:40 with the wild-type enzyme and the mutant enzymes R54Q, E58D and E125Q. With the mutants R54Q, E58D and E125Q, releasing ATP is increased to 70% of total hydrolysis. Activity of mutants E55Q, E59D and E59Q is to low to be detected
-
-
?
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A + H2O
2 alpha,beta-oxymethylene-ADP
show the reaction diagram
-
diadenosine polyphosphate analog
-
-
?
Ap4A + H2O
?
show the reaction diagram
-
-
-
-
?
betabeta'-methyleneoxy-Ap4A + H2O
AMP + beta,gamma-methyleneoxy-ATP
show the reaction diagram
-
diadenosine polyphosphate analog
-
-
?
diadenosine 5',5''-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
diadenosine 5',5'-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
diadenosine 5',5'-P1,P4-tetraphosphate + H2O
ATP + AMP
show the reaction diagram
-
-
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
-
5 mM MgCl2 included in assay medium
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1,4-dihydroxy-5,8-bis[(4-methylphenyl)amino]anthracene-9,10-dione
NSC86169
2-((8-hydroxy-4-(4-methyl-2-sulfoanilino)-9,10-dioxo-9,10-dihydro-1-anthracenyl)amino)-5-methylbenzenesulfonic acid
NSC51531, competitive inhibitor
2-[2-[(4-aminophenyl)amino]-6-phenylpyrimidin-4-yl]phenol
NSC232476
5-hydroxy-1,4-bis[(4-methylphenyl)amino]anthracene-9,10-dione
NSC300513
5-methyl-2-[[4-(methylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino]benzenesulfonate
NSC401611
perylene-3,4,9,10-tetracarboxylic acid
NSC89768
1,2,3,4-tetra(adenosine-5'-O-phosphorothio)erythritol
-
-
1,2,3-tri(adenosine-5'-O-phosphorothio)glycerol
-
-
1,3-di(adenosine-5'-O-phospho)-2-phosphorothio-glycerol
-
-
1,4-di(adenosine-5'-O-phospho)erythritol
-
-
1,4-di(adenosine-5'-O-phosphorothio)erythritol
-
-
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A
-
competitive inhibitor
A-5'-p-beta,beta'-methyleneoxy-p-5'-A
-
competitive inhibitor
additional information
NSC113427, NSC133815, and NSC305522, do not exhibit any enzyme inhibition at concentrations in excess of 0.1 mM
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.12 - 10
Ap4A
0.0025
diadenosine 5',5'-P1,P4-tetraphosphate
-
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00031 - 40.8
Ap4A
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00109
2-((8-hydroxy-4-(4-methyl-2-sulfoanilino)-9,10-dioxo-9,10-dihydro-1-anthracenyl)amino)-5-methylbenzenesulfonic acid
in 100 mM Tris-acetate, pH 7.7, 5 mM magnesium acetate, and 5% DMSO, at 25°C
0.005
2-[2-[(4-aminophenyl)amino]-6-phenylpyrimidin-4-yl]phenol
Ki about 0.005 mM, in 100 mM Tris-acetate, pH 7.7, 5 mM magnesium acetate, and 5% (v/v) DMSO, at 25°C
0.00289
5-methyl-2-[[4-(methylamino)-9,10-dioxo-9,10-dihydroanthracen-1-yl]amino]benzenesulfonate
in 100 mM Tris-acetate, pH 7.7, 5 mM magnesium acetate, and 5% (v/v) DMSO, at 25°C
0.013
1,2,3,4-tetra(adenosine-5'-O-phosphorothio)erythritol
-
pH 7.6, 30°C
0.017
1,2,3-tri(adenosine-5'-O-phosphorothio)glycerol
-
pH 7.6, 30°C
0.025
1,3-di(adenosine-5'-O-phospho)-2-phosphorothio-glycerol
-
pH 7.6, 30°C
0.0085
1,4-di(adenosine-5'-O-phospho)erythritol
-
pH 7.6, 30°C
0.00015
1,4-di(adenosine-5'-O-phosphorothio)erythritol
-
pH 7.6, 30°C
0.0015
A-5'-p-alpha,beta,alpha',beta'-bis(oxymethylene)p-5'-A
-
-
0.0022
A-5'-p-beta,beta'-methyleneoxy-p-5'-A
-
-
0.003 - 1
F-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7.6
-
assay at
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
O04841_LUPAN
199
0
22982
TrEMBL
Mitochondrion (Reliability: 3)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
19120
-
wild-type enzyme, MALDI-MS
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E122Q
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. KM-value is 20% of the wild-type value, turnover-number is 50% of the wild-type value. 2.3fold reduction in sensitivity to fluoride
E125Q
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser. KM-value is 0.7% of the wild-type value, turnover-number is 56% of the wild-type value. Cleavage of (2'-pdA)AppppA to produce ATP and 2'-deoxyadenylated AMP rather than 2'-deoxyadenylated ATP + AMP as with wild-type enzyme, the ratio of ATP released is increased compared to wild-type. 83fold reduction in sensitivity to fluoride
E55Q
-
fusion protein containing and N-terminal extension of Gly-Pro-Leu-Gly-Ser. KM-value is 4.8% of the wild-type value, turnover-number is 0.01% of the wild-type value. Activity with (2'-pdA)AppppA is to low to be detected. More than 330fold reduction in sensitivity to fluoride
E58D
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. KM-value is 38.4% of the wild-type value, turnover-number is 9% of the wild-type value. Cleavage of (2'-pdA)AppppA to produce ATP and 2'-deoxyadenylated AMP rather than 2'-deoxyadenylated ATP + AMP as with wild-type enzyme, the ratio of ATP released is increased compared to wild-type. 16.7fold reduction in sensitivity to fluoride
E58Q
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. KM-value is 80% of the wild-type value, turnover-number is 43.9% of the wild-type value. 6.7fold reduction in sensitivity to fluoride
E59D
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. KM-value is 4fold higher than the wild-type value, turnover-number is 0.02% of the wild-type value. Activity with (2'-pdA)AppppA is to low to be detected. 2fold reduction in sensitivity to fluoride
E59Q
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. KM-value is 2.4fold higher than the wild-type value, turnover-number is 0.00076% of the wild-type value. Activity with (2'-pdA)AppppA is to low to be detected
R54Q
-
fusion protein containing and N-terminal extension Gly-Pro-Leu-Gly-Ser-Pro-Asn-Cys. Cleavage of (2'-pdA)AppppA to produce ATP and 2'-deoxyadenylated AMP rather than 2'-deoxyadenylated ATP + AMP as with wild-type enzyme, the ratio of ATP released is increased compared to wild-type. 330fold reduction in sensitivity to fluoride
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
symmetrical Ap4A hydrolase is partially purified from Escherichia coli
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Maksel, D.; Gooley, P.R.; Swarbrick, J.D.; Guranowski, A.; Gange, C.; Blackburn, G.M.; Gayler, K.R.
Characterization of active-site residues in diadenosine tetraphosphate hydrolase from Lupinus angustifolius
Biochem. J.
357
399-405
2001
Lupinus angustifolius
Manually annotated by BRENDA team
Guranowski, A.; Starzynska, E.; McLennan, A.G.; Baraniak, J.; Stec, W.J.
Adenosine-5'-O-phosphorylated and adenosine-5'-O-phosphorothioylated polyols as strong inhibitors of (symmetrical) and (asymmetrical) dinucleoside tetraphosphatases
Biochem. J.
373
635-640
2003
Homo sapiens, Lupinus angustifolius
Manually annotated by BRENDA team
Guranowski, A.; Starzynska, E.; Pietrowska-Borek, M.; Rejman, D.; Blackburn, G.M.
Novel diadenosine polyphosphate analogs with oxymethylene bridges replacing oxygen in the polyphosphate chain: potential substrates and/or inhibitors of Ap4A hydrolases
FEBS J.
276
1546-1553
2009
Homo sapiens, Lupinus angustifolius
Manually annotated by BRENDA team
Branson, K.M.; Mertens, H.D.; Swarbrick, J.D.; Fletcher, J.I.; Kedzierski, L.; Gayler, K.R.; Gooley, P.R.; Smith, B.J.
Discovery of inhibitors of lupin diadenosine 5,5-P1,P4-tetraphosphate hydrolase by virtual screening
Biochemistry
48
7614-7620
2009
Lupinus angustifolius (O04841)
Manually annotated by BRENDA team