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Literature summary for 2.1.1.45 extracted from

  • Phan, J.; Mahdavian, E.; Nivens, M.C.; Minor, W.; Berger, S.; Spencer, H.T.; Dunlap, R.B.; Lebioda, L.
    Catalytic cysteine of thymidylate synthase is activated upon substrate binding (2000), Biochemistry, 39, 6969-6978.
    View publication on PubMed

Application

Application Comment Organism
medicine enzyme is believed to be the major site of the cytotoxic action of the cancer chemotherapeutic drug 5-fluorouracil, development of inhibitors as clinical useful drugs Homo sapiens
medicine enzyme is believed to be the major site of the cytotoxic action of the cancer chemotherapeutic drug 5-fluorouracil, development of inhibitors as clinical useful drugs Lacticaseibacillus casei
medicine human TS mutants have potential applications in gene therapy by protecting hematopoietic progenitors from TS inhibitor toxicity, drug-resistant variants can be used to decrease the myelosuppressive side effects of TS-directed anticancer agents or to select genetically modified cells in vivo, clincal trials introduce chemoprotecting genes into hematopoietic cells Homo sapiens

Cloned(Commentary)

Cloned (Comment) Organism
bacterial expression vector for overproduction in Escherichia coli Homo sapiens
Escherichia coli NM522 cells used for cloning and library construction, Escherichia coli chi2913recA lacking TS used for expression by complementation Homo sapiens

Crystallization (Commentary)

Crystallization (Comment) Organism
crystallized in the I2(1)3 space group Escherichia coli
crystals grown by vapor diffusion method in hanging drop setup Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.0011
-
2'-deoxyuridylate wild-type Escherichia coli
0.0053
-
2'-deoxyuridylate mutant S167A Escherichia coli
0.0081
-
methylenetetrahydrofolate wild-type Escherichia coli
0.0085
-
methylenetetrahydrofolate wild-type Escherichia coli
0.0097
-
5-bromo-2'-deoxyuridine wild-type Escherichia coli
0.0097
-
methylenetetrahydrofolate mutant S167A Escherichia coli
0.012
-
methylenetetrahydrofolate mutant S167A Escherichia coli
0.0339
-
2'-deoxyuridylate mutant S167G Escherichia coli
0.0417
-
2'-deoxyuridylate mutant S167T Escherichia coli
0.0426
-
methylenetetrahydrofolate mutant S167G Escherichia coli
0.0521
-
methylenetetrahydrofolate mutant S167T Escherichia coli
0.0627
-
methylenetetrahydrofolate mutant S167T Escherichia coli
0.0723
-
5-bromo-2'-deoxyuridine mutant S167A Escherichia coli
0.0981
-
2'-deoxyuridylate mutant S167C Escherichia coli
0.13
-
methylenetetrahydrofolate mutant S167C Escherichia coli
0.514
-
5-bromo-2'-deoxyuridine mutant S167G Escherichia coli

Molecular Weight [Da]

Molecular Weight [Da] Molecular Weight Maximum [Da] Comment Organism
35000
-
2 * 35000, SDS-PAGE Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
5,10-methylenetetrahydrofolate + dUMP Homo sapiens
-
dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + dUMP Lacticaseibacillus casei
-
dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + dUMP Escherichia coli
-
dihydrofolate + dTMP
-
?

Organism

Organism UniProt Comment Textmining
Escherichia coli P0A884
-
-
Homo sapiens
-
human colorectal tumor cell line C
-
Lacticaseibacillus casei
-
-
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
5,10-methylene-5,6,7,8-tetrahydrofolate + dUMP
-
Escherichia coli 7,8-dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + 5-bromo-2'-deoxyuridine
-
Escherichia coli ?
-
?
5,10-methylenetetrahydrofolate + dUMP
-
Homo sapiens dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + dUMP
-
Homo sapiens dihydrofolate + dTMP
-
r
5,10-methylenetetrahydrofolate + dUMP
-
Lacticaseibacillus casei dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + dUMP
-
Lacticaseibacillus casei dihydrofolate + dTMP
-
r
5,10-methylenetetrahydrofolate + dUMP
-
Escherichia coli dihydrofolate + dTMP
-
?
5,10-methylenetetrahydrofolate + dUMP
-
Escherichia coli dihydrofolate + dTMP
-
r
5-bromo-2'-deoxyuridine 5'-monophosphate + ? dehalogenation does not require methylenetetrahydrofolate as cosubstrate Escherichia coli ?
-
?

Subunits

Subunits Comment Organism
dimer
-
Lacticaseibacillus casei
dimer
-
Escherichia coli
dimer 2 * 35000, SDS-PAGE Homo sapiens