Literature summary for 6.3.2.17 extracted from

Zhao, R.; Titus, S.; Gao, F.; Moran, R.G.; Goldman, I.D.
Molecular analysis of murine leukemia cell lines resistant to 5,10-dideazatetrahydrofolate identifies several amino acids critical to the function of folylpolyglutamate synthetase (2000), J. Biol. Chem., 275, 26599-26606.

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Cloned(Commentary)

Cloned (Comment)	Organism
expression of wild type and mutant enzymes in AUXB1 cell line, which does not express measurable enzyme activity and is auxotrophic for the products of folate metabolism	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
A337V	L44 cells	Mus musculus
G178E	L7 cells	Mus musculus
G320D	L15 cells	Mus musculus
S180F	L51 cells	Mus musculus
S67F	L51 cells	Mus musculus
S67F	L7 cells	Mus musculus
T339I	L44 cells	Mus musculus
W445stop	L15 cells	Mus musculus

Inhibitors

Inhibitors	Comment	Organism	Structure
5,10-dideaza-5,6,7,8-tetrahydrofolic acid	lometrexo, used to generate the 5,10-dideazatetrahydrofolate resistant cells sublines	Mus musculus
methotrexate	the level required to inhibit the 5,10-dideazatetrahydrofolate resistant cell sublines is unchanged or slightly decreased compared with wild type cells	Mus musculus
N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid	raltitrexed, no inhibition observed with the 5,10-dideazatetrahydrofolate resistant cells sublines	Mus musculus
pemetrexed disodium	ALIMTA, no inhibition observed with the 5,10-dideazatetrahydrofolate resistant cells sublines	Mus musculus

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	-	mouse	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
L-1210 cell	leukemia line, wild type and L7, L15, L44 and L51 5,10-dideazatetrahydrofolate resistant cells sublines	Mus musculus	-

Specific Activity [micromol/min/mg]

Specific Activity Minimum [µmol/min/mg]	Specific Activity Maximum [µmol/min/mg]	Comment	Organism
0.00000006	-	enzyme from L44 cells	Mus musculus
0.0000001	-	enzyme from L15 cells	Mus musculus
0.0000001	-	enzyme from L51 cells	Mus musculus
0.0000001	-	enzyme from L7 cells	Mus musculus
0.000008	-	wild type enzyme	Mus musculus

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + 5,10-dideaza-5,6,7,8-tetrahydrofolic acid + L-glutamate	-	Mus musculus	ADP + 5,10-dideaza-5,6,7,8-tetrahydrofolyl-L-Glu + phosphate	-	?
ATP + 5-formyl-5,6,7,8-tetrahydrofolate + L-glutamate	-	Mus musculus	ADP + 5-formyl-5,6,7,8-tetrahydrofolyl-L-Glu + phosphate	-	?
ATP + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)glutamic acid + L-glutamate	folic acid	Mus musculus	ADP + phosphate + N-(p(((2-amino-4-hydroxy-6-pteridinyl)methyl)-amino)benzoyl)-Glu2	-	?

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Release 2023.1 (January 2023)