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Information on EC 3.6.1.28 - thiamine-triphosphatase and Organism(s) Homo sapiens and UniProt Accession Q9BU02

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     3 Hydrolases
         3.6 Acting on acid anhydrides
             3.6.1 In phosphorus-containing anhydrides
                3.6.1.28 thiamine-triphosphatase
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This record set is specific for:
Homo sapiens
UNIPROT: Q9BU02 not found.
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The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Synonyms
thiamine triphosphatase, thtpase, ttpase, thtpa, 25-kda thiamine triphosphatase, 25 kda thiamine triphosphatase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
25-kDa thiamine triphosphatase
-
phosphatase, thiamine tri-
-
-
-
-
thiamine triphosphatase
Thtpa
-
-
ThTPase
-
-
-
-
TTPase
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
phosphoric ester hydrolysis
-
-
-
-
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
thiamine-triphosphate phosphohydrolase
-
CAS REGISTRY NUMBER
COMMENTARY hide
9068-47-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
thiamine triphosphate + H2O
thiamine diphosphate + phosphate
show the reaction diagram
ATP + H2O
ADP + phosphate
show the reaction diagram
-
the catalytic efficiency is about 4 orders of magnitude lower than for thiamine triphosphate
-
-
?
thiamine triphosphate + H2O
thiamine diphosphate + phosphate
show the reaction diagram
-
-
-
-
?
additional information
?
-
-
Thtpa is known to decrease the levels of the energy currency molecule, thiamine triphosphate
-
-
?
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
additional information
?
-
-
Thtpa is known to decrease the levels of the energy currency molecule, thiamine triphosphate
-
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Mg2+
enzyme is 5% active in the absence of Mg2+
Mn2+
0.1 mM
Zn2+
in the presence of Mg2+ at pH 8
Mg2+
-
required
Zn2+
-
inhibits at micromolar concentrations at pH 8.0, activates at pH 6.0
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
([2-[3-(4-Amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-thiazol-5-yl]-ethoxy]-phosphonomethyl-phosphinoylmethyl)-phosphonic acid
-
-
5,5'-dithiobis-2-nitrobenzoic acid
-
thiamine triphosphate
-
-
Zn2+
pH 8.5, IC50: 0.007 mM
([2-[3-(4-Amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-thiazol-5-yl]-ethoxy]-phosphonomethyl-phosphinoylmethyl)-phosphonic acid
-
-
ATP
-
very poor inhibitor
Ca2+
-
inhibits by competition with Mg2+
SDS
-
IC50: about 0.3% W/v. The inhibition is partially reversible, probably due to correct refolding of the denatured enzyme
Zn2+
-
inhibits at micromolar concentrations at pH 8.0, IC50: about 0.015-0.02 mM. Activates at pH 6.0
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
additional information
-
overexpression of N-myc downstream regulated gene-1, Ndrg-1, leads to upregulation of Thtpa in cancer cells, overview
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.126 - 0.25
thiamine triphosphate
3.7
ATP
-
in presence of 8 mM ATP
0.126
thiamin triphosphate
-
-
0.056 - 0.154
thiamine triphosphate
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
240
thiamine triphosphate
-
0.24
ATP
-
in presence of 8 mM Mg2+
140
thiamine triphosphate
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
1.2
([2-[3-(4-Amino-2-methyl-pyrimidin-5-ylmethyl)-4-methyl-thiazol-5-yl]-ethoxy]-phosphonomethyl-phosphinoylmethyl)-phosphonic acid
-
-
0.03 - 0.15
Ca2+
0.95
thiamine triphosphate
-
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.007
Zn2+
Homo sapiens
pH 8.5, IC50: 0.007 mM
0.015 - 0.02
Zn2+
Homo sapiens
-
inhibits at micromolar concentrations at pH 8.0, IC50: about 0.015-0.02 mM. Activates at pH 6.0
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.057
-
cerebellum
225
pure untagged recombinant thiamine triphosphatase, 37°C, pH 8.2
4.5
wild type thiamine triphosphatase from supernatant
140
-
purified recombinant enzyme
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
8.5
wild type enzyme
9.4
GST-fused E63Q mutant enzyme
pH RANGE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
7 - 9.5
-
pH 7.0: about 60% of maximal activity, pH 9.5: about 75% of maximal activity
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
low activity
Manually annotated by BRENDA team
high activity
Manually annotated by BRENDA team
high activity
Manually annotated by BRENDA team
high activity
Manually annotated by BRENDA team
-
cerebral cortex
Manually annotated by BRENDA team
-
non-metastatic human colorectal adenocarcinoma cells
Manually annotated by BRENDA team
-
metastatic lung cancer cells
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
-
-
-
Manually annotated by BRENDA team
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
THTPA_HUMAN
230
0
25566
Swiss-Prot
other Location (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
23892
1 * 23892, mass spectrometry
25000
27000
1 * 27000, SDS-PAGE
25550
-
gel filtration
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
monomer
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
complex with tripolyphosphate, to 2.3 A resolution and docking solution of substrate thiamine triphosphate. The thiazole ring of the thiamine forms a stacking interaction with Trp53, and the aminopyrimidine ring lies in a pocket defined by His76, Pro191 and Ile195. The triphosphate moiety occupies a similar position as in the enzyme-tripolyphosphate complex, with interactions involving the side chains of Lys11, Arg55, Arg57, Lys65, Arg125 and Lys193
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
E63Q
reduced activity
E78K
reduced activity
E85K
reduced activity
additional information
-
overexpression of N-myc downstream regulated gene-1, Ndrg-1, leads to upregulation of Thtpa in cancer cells, overview
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
5
GST-tagged wild type enzyme activity was nearly zero at pH 5.0
55 - 60
-
30 min, stable
68
-
30 min, 50% loss of activity
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
MagneGST Protein Purification System, only mutated enzymes expressed as GST fusion proteins
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expressed in Escherichia coli strain BL21
overexpression in Escherichia coli as a glutathione S-transferase fusion protein
expression analysis
-
expression in Escherichia coli, the recombinant enzyme is completely functional
-
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Bettendorff, L.; Mastrogiacomo, F.; Kish, S.J.; Grisar, T.
Thiamine, thiamine phosphates, and their metabolizing enzymes in human brain
J. Neurochem.
66
250-258
1996
Homo sapiens
Manually annotated by BRENDA team
Makarchikov, A.F.; Lakaye, B.; Gulyai, I.E.; Czerniecki, J.; Coumans, B.; Wins, P.; Grisar, T.; Bettendorff, L.
Thiamine triphosphate and thiamine triphosphatase activities: from bacteria to mammals
Cell. Mol. Life Sci.
60
1477-1488
2003
Bos taurus, Gallus gallus, Homo sapiens, quail, Rattus norvegicus, Sus scrofa
Manually annotated by BRENDA team
Lakaye, B.; Makarchikov, A.F.; Wins, P.; Margineanu, I.; Roland, S.; Lins, L.; Aichour, R.; Lebeau, L.; El Moualij, B.; Zorzi, W.; Coumans, B.; Grisar, T.; Bettendorff, L.
Human recombinant thiamine triphosphatase: purification, secondary structure and catalytic properties
Int. J. Biochem. Cell Biol.
36
1348-1364
2004
Homo sapiens
Manually annotated by BRENDA team
Lakaye, B.; Makarchikov, A.F.; Antunes, A.F.; Zorzi, W.; Coumans, B.; De Pauw, E.; Wins, P.; Grisar, T.; Bettendorff, L.
Molecular characterization of a specific thiamine triphosphatase widely expressed in mammalian tissues
J. Biol. Chem.
277
13771-13777
2002
Bos taurus (Q8MKF1), Bos taurus, Homo sapiens (Q9BU02), Homo sapiens
Manually annotated by BRENDA team
Szyniarowski Piot, S.P.; Lakaye Bernar, L.B.; Czerniecki Ja, C.J.; Makarchikov Alexander , M.A.; Wins Pierr, W.P.; Margineanu Ilc, M.I.; Coumans Bernar, C.B.; Grisar Thierr, G.T.; Bettendorff Lucie, B.L.
Pig tissues express a catalytically inefficient 25-kDa thiamine triphosphatase: insight in the catalytic mechanisms of this enzyme
Biochim. Biophys. Acta
1725
93-102
2005
Homo sapiens (Q9BU02), Homo sapiens, Sus scrofa
Manually annotated by BRENDA team
Kovacevic, Z.; Fu, D.; Richardson, D.R.
The iron-regulated metastasis suppressor, Ndrg-1: identification of novel molecular targets
Biochim. Biophys. Acta
1783
1981-1992
2008
Homo sapiens, Rattus norvegicus (Q8CGV7)
Manually annotated by BRENDA team
Delvaux, D.; Kerff, F.; Murty, M.R.; Lakaye, B.; Czerniecki, J.; Kohn, G.; Wins, P.; Herman, R.; Gabelica, V.; Heuze, F.; Tordoir, X.; Maree, R.; Matagne, A.; Charlier, P.; De Pauw, E.; Bettendorff, L.
Structural determinants of specificity and catalytic mechanism in mammalian 25-kDa thiamine triphosphatase
Biochim. Biophys. Acta
1830
4513-4523
2013
Mus musculus (Q8JZL3), Homo sapiens (Q9BU02)
Manually annotated by BRENDA team