Literature summary for 2.1.1.45 extracted from

Fantz, C.; Shaw, D.; Jennings, W.; Forsthoefel, A.; Kitchens, M.; Phan, J.; Minor, W.; Lebioda, L.; Berger, F.G.; Spencer, H.T.
Drug-resistant variants of Escherichia coli thymidylate synthase: effects of substitutions at Pro-254 (2000), Mol. Pharmacol., 57, 359-366.

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Application

Application	Comment	Organism
medicine	-	Mus musculus
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
mutant P254D cDNA cloned into SacII/XhoI sites of the HaMSV retroviral vector and transfected into the TS negative cell line RJK88.13	Homo sapiens

Crystallization (Commentary)

Crystallization (Comment)	Organism
-	Escherichia coli
mutant P254S	Homo sapiens

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism	Structure
0.001	-	methylenetetrahydropteroylgluamate	mutant P254S	Escherichia coli
0.0011	-	methylenetetrahydropteroylgluamate	wild-type	Escherichia coli
0.0012	-	2'-deoxyuridylate	wild-type	Escherichia coli
0.0012	-	methylenetetrahydropteroylgluamate	mutant P254G	Escherichia coli
0.0015	-	2'-deoxyuridylate	mutant P254G	Escherichia coli
0.0018	-	2'-deoxyuridylate	mutant P254F	Escherichia coli
0.0018	-	methylenetetrahydropteroylgluamate	mutant P254F	Escherichia coli
0.0027	-	2'-deoxyuridylate	mutant P254S	Escherichia coli
0.0034	-	2'-deoxyuridylate	mutant P254D	Escherichia coli
0.0118	-	methylenetetrahydropteroylgluamate	mutant P254D	Escherichia coli

Natural Substrates/ Products (Substrates)

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

Organism

Organism	UniProt	Comment	Textmining
Escherichia coli	P0A884	-	-
Homo sapiens	-	human	-
Mus musculus	-	-	-

Purification (Commentary)

Purification (Comment)	Organism
-	Escherichia coli
Pro-254 mutant enzymes	Homo sapiens

Source Tissue

Source Tissue	Comment	Organism	Textmining
bone marrow	-	Mus musculus	-
bone marrow	-	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
5,10-methylenetetrahydrofolate + dUMP	-	Mus musculus	dihydrofolate + dTMP	-	?
5,10-methylenetetrahydrofolate + dUMP	-	Mus musculus	dihydrofolate + dTMP	-	r
5,10-methylenetetrahydrofolate + dUMP	-	Homo sapiens	dihydrofolate + dTMP	-	?
5,10-methylenetetrahydrofolate + dUMP	-	Homo sapiens	dihydrofolate + dTMP	-	r
5,10-methylenetetrahydrofolate + dUMP	-	Escherichia coli	dihydrofolate + dTMP	-	?
5,10-methylenetetrahydrofolate + dUMP	-	Escherichia coli	dihydrofolate + dTMP	-	r
methylenetetrahydropteroylglutamate + dUMP	-	Escherichia coli	7,8-dihydropteroylglutamate + thymidine phosphate	-	r

Temperature Stability [°C]

Temperature Stability Minimum [°C]	Temperature Stability Maximum [°C]	Comment	Organism
37	-	half-life of wild-type enzyme is 90 min, half-life of mutants P254F, P254S and P254D are approximately 50 min	Homo sapiens

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Release 2023.1 (January 2023)