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Information on EC 2.1.1.67 - thiopurine S-methyltransferase and Organism(s) Mus musculus and UniProt Accession O55060

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EC Tree
     2 Transferases
         2.1 Transferring one-carbon groups
             2.1.1 Methyltransferases
                2.1.1.67 thiopurine S-methyltransferase
IUBMB Comments
Also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase.
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This record set is specific for:
Mus musculus
UNIPROT: O55060
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The taxonomic range for the selected organisms is: Mus musculus
The expected taxonomic range for this enzyme is: Bacteria, Eukaryota, Archaea
Synonyms
thiopurine methyltransferase, thiopurine s-methyltransferase, thiopurine methyl transferase, thiopurine-s-methyl-transferase, s-adenosyl-l-methionine:thiopurine s-methyltransferase, 6-thiopurine s-methyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
thiopurine S-methyltransferase
-
6-thiopurine transmethylase
-
-
-
-
mercaptopurine methyltransferase
-
-
-
-
thiopurine methyltransferase
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
methyl group transfer
-
methyl group transfer
PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:thiopurine S-methyltransferase
Also acts, more slowly, on thiopyrimidines and aromatic thiols. Not identical with EC 2.1.1.9 thiol S-methyltransferase.
CAS REGISTRY NUMBER
COMMENTARY hide
67339-09-7
-
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + 2,8-dihydroxy-6-thiopurine
S-adenosyl-L-homocysteine + 2,8-dihydroxy-6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-amino-6-thiopurine
S-adenosyl-L-homocysteine + 2-amino-6-methylthiopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiothymine
S-adenosyl-L-homocysteine + 2-methylthiothymine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 2-thiouracil
S-adenosyl-L-homocysteine + thiouracil-2-S-methylether
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-mercaptopurine
S-adenosyl-L-homocysteine + 6-methylmercaptopurine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thioguanine
S-adenosyl-L-homocysteine + 6-methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + 6-thiopurine
S-adenosyl-L-homocysteine + 6-methylthiopurine
show the reaction diagram
-
preferred substrate
-
-
?
S-adenosyl-L-methionine + 6-thiouric acid
S-adenosyl-L-homocysteine + 6-methylthiouric acid
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
S-adenosyl-L-methionine + azathioprine
?
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioguanine nucleotide
S-adenosyl-L-homocysteine + methylthioguanine
show the reaction diagram
-
-
-
-
?
S-adenosyl-L-methionine + thioinosine monophosphate
S-adenosyl-L-homocysteine + methylthioinosine monophosphate
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
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
-
-
-
?
S-adenosyl-L-methionine + a thiopurine
S-adenosyl-L-homocysteine + a thiopurine S-methylether
show the reaction diagram
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
2,3-Dithiopropanol
-
-
2,4-dithiopyrimidine
-
-
2-amino-6-thiopurine
-
-
2-mercaptoethanol
-
-
2-methylthio-4-hydroxypyrimidine
-
1.8 mM, 45% inhibition
2-Methylthiouracil
-
-
5-methyl-2,4-dithiopyrimidine
-
-
6-hydroxy-2-thiopurine
-
-
6-methylthiopurine
-
-
glutathione
-
-
L-cysteine
-
1.8 mM, 50% inhibition
L-homocysteine
-
-
L-homocysteine thiolactone
-
-
S-adenosyl-L-methionine
-
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.00035
6-Mercaptopurine
-
0.0056
S-adenosyl-L-methionine
-
1.7
2-Thiouracil
-
-
0.2
6-Thiopurine
-
-
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
6.5
TPMT activity assay
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
37
TPMT activity assay
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
primary cell
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
-
when thiopurine methyltransferase protein activity is low a greater degree of cytotoxicity and DNA damage can occur after thioguanine exposure
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
TPMT_MOUSE
240
0
27586
Swiss-Prot
other Location (Reliability: 1)
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
two crystal structures of murine TPMT are determined, as a binary complex with the product S-adenosyl-L-homocysteine and as a ternary complex with S-adenosyl-L-homocysteine and the substrate 6-mercaptopurine, to 1.8 and 2.0 A resolution, respectively
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
45 - 56
-
heat inactivation, 23% of the activity is lost after 20 min at 45°C, 95% activity is lost after 6 min at 56°C
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
using a Ni2+-NTA resin and a gel-filtration column
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
cDNA cloned and heterologous expressed in rabbit reticulocytes and wheat germ lysate
the full-length coding region is amplified by PCR from a eukaryotic expression plasmid and cloned into the pET-28a vector for expression in Escherichia coli BL21DE3 cells
a 8.7 kb fragment encompassing part of exon III through a portion of intron 6 is subcloned into the pZERO-2 vector
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
thiopurine S-methyltransferase modulates the cytotoxic effects of thiopurine prodrugs such as 6-mercaptopurine by methylating them in a reaction using S-adenosyl-L-methionine as the donor
medicine
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Remy, C.N.
Metabolism of thiopyrimidines and thiopurines
J. Biol. Chem.
238
1078-1084
1963
Mus musculus, Rattus norvegicus, Mus musculus Swiss-Webster
Manually annotated by BRENDA team
Van Loon, J.A.; Weinshilboum, R.M.
Thiopurine methyltransferase isozymes in human renal tissue
Drug Metab. Dispos.
18
632-638
1990
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Szumlanski, C.L.; Honchel, R.; Scott, M.C.; Weinshilboum, R.M.
Human liver thiopurine methyltransferase pharmacogenetics: biochemical properties, liver-erythrocyte correlation and presence of isozymes
Pharmacogenetics
2
148-159
1992
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Fessing, M.Y.; Belkov, V.M.; Krynetski, E.Y.; Evans, W.E.
Molecular cloning and functional characterization of the cDNA encoding the murine thiopurine S-methyltransferase (TPMT)
FEBS Lett.
424
143-145
1998
Homo sapiens, Mus musculus (O55060), Mus musculus
Manually annotated by BRENDA team
Dervieux, T.; Blanco, J.G.; Krynetski, E.Y.; Vanin, E.F.; Roussel, M.F.; Relling, M.V.
Differing contribution of thiopurine methyltransferase to mercaptopurine versus thioguanine effects in human leukemic cells
Cancer Res.
61
5810-5816
2001
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Peng, Y.; Feng, Q.; Wilk, D.; Adjei, A.A.; Salavaggione, O.E.; Weinshilboum, R.M.; Yee, V.C.
Structural basis of substrate recognition in thiopurine s-methyltransferase
Biochemistry
47
6216-6225
2008
Mus musculus (O55060), Mus musculus, Homo sapiens (P51580), Homo sapiens
Manually annotated by BRENDA team
Hartford, C.; Vasquez, E.; Schwab, M.; Edick, M.J.; Rehg, J.E.; Grosveld, G.; Pui, C.H.; Evans, W.E.; Relling, M.V.
Differential effects of targeted disruption of thiopurine methyltransferase on mercaptopurine and thioguanine pharmacodynamics
Cancer Res.
67
4965-4972
2007
Mus musculus
Manually annotated by BRENDA team
Hosni-Ahmed, A.; Barnes, J.D.; Wan, J.; Jones, T.S.
Thiopurine methyltransferase predicts the extent of cytotoxicty and DNA damage in astroglial cells after thioguanine exposure
PLoS ONE
6
e29163
2011
Homo sapiens, Mus musculus
Manually annotated by BRENDA team