6.3.2.17	(2S)-2-(o-fluoro-p-(N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-N-(prop-2-ynyl-amino)benzamido)-4-(tetrazol-5-yl)butyric acid	IC50 of 0.0000153 mM in the wild type cell line, IC50 of 0.000008 mM to 0.0016 mM in the antifolates-resistant sublines	13522	
6.3.2.17	(2S)-2-(o-fluoro-p-(N-(2,7-dimethyl-4-oxo-3,4-dihydroquinazolin-6-yl)methyl)-N-(prop-2-ynyl-amino)benzamido)-4-(tetrazol-5-yl)butyric acid	IC50 of 0.0000125 mM in the wild type cell line, IC50 of 0.0000635 mM in the MTA-13 cell line	13522	
6.3.2.17	(6R)-10-formyl-5,6,7,8-tetrahydropteroylpentaglutamate	-	17308	
6.3.2.17	(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate	-	17800	
6.3.2.17	(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate	-	23569	
6.3.2.17	(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate	-	17802	
6.3.2.17	(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate	-	17803	
6.3.2.17	(6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate	-	17819	
6.3.2.17	(6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate	-	23568	
6.3.2.17	(6S)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate	-	17801	
6.3.2.17	(6S)-5,10-methylene-5,6,7,8-tetrahydropteroylpentaglutamate	-	17309	
6.3.2.17	(6S)-5,6,7,8-tetrahydropteroylpentaglutamate	-	17307	
6.3.2.17	(6S)-5-formyl-5,6,7,8-tetrahydropteroylpentaglutamate	-	33883	
6.3.2.17	(6S)-5-methyl-5,6,7,8-tetrahydropteroylpentaglutamate	-	33882	
6.3.2.17	(NH4)2SO4	-	399	
6.3.2.17	(S)-2(5-(((1,2-dihydro-3-methyl-1-oxobenzo-(f)quinazolin-9-yl)methyl)-1-oxo-2-isoindolinyl))-glutaric acid	IC50 of 0.0000009 mM in the wild type cell line, IC50 of 0.0000012 mM to 0.000539 mM in the antifolates-resistant sublines	54686	
6.3.2.17	2,4-Diamino-pteroyl-Orn	-	90819	
6.3.2.17	2-Amino-4-oxo-5,8-dideazapteroyl-Orn	-	90932	
6.3.2.17	2-[[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]phenyl)(hydroxy)phosphoryl]methyl]pentanedioic acid	-	12072	
6.3.2.17	2-[[[(3S)-3-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-3-carboxypropyl](hydroxy)phosphoryl]methyl]pentanedioic acid	-	19160	
6.3.2.17	2-[[[(4S)-4-carboxy-4-[(4-[[(2,4-diaminopteridin-6-yl)methyl](methyl)amino]benzoyl)amino]butyl](hydroxy)phosphoryl]methyl]pentanedioic acid	-	78433	
6.3.2.17	2-[[[(4S)-4-[(4-[2-[(6R)-2-amino-4-oxo-3,4,5,6,7,8-hexahydropyrido[2,3-d]pyrimidin-6-yl]ethyl]benzoyl)amino]-4-carboxybutyl](hydroxy)phosphoryl]methyl]pentanedioic acid	-	78436	
6.3.2.17	2-[[[(4S)-4-[(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)amino]-4-carboxybutyl](hydroxy)phosphoryl]methyl]pentanedioic acid	-	78434	
6.3.2.17	3,3-Difluoroglutamic acid	i.e. beta,beta-difluoroglutamate, , the effect on polyglutamylation is dependent on its position relative to the point of L-Glu ligation. When beta,beta-difluoroglutamate is the acceptor amino acid, i.e. point of attachment. Ligation of Glu is enhanced. When beta,beta-difluoroglutamate is one residue distal to the acceptor amino acid, further elongation is blocked	43237	
6.3.2.17	3-(N-phosphonoacetyl)amino-2-L-(N-pteroylamino)propanoic acid	slight inhibition at 0.1 mM	54688	
6.3.2.17	3-N-(methoxyphosphono)acetylamino-2-L-(N-pteroylamino)propanoic acid	slight inhibition at 0.1 mM	54689	
6.3.2.17	4-amino-4-deoxypteroyl-L-ornithine	-	33885	
6.3.2.17	4-threo-Fluoroglutamate	prevents or severly retards further addition of Glu	95967	
6.3.2.17	5,10-dideaza-5,6,7,8-tetrahydrofolic acid	IC50 of 0.0000277 mM in the wild type cell line, IC50 of 0.000143 mM to 0.0035 mM in the antifolates-resistant sublines	11365	
6.3.2.17	5,10-dideaza-5,6,7,8-tetrahydrofolic acid	IC50 of 0.0000591 mM in the wild type cell line, IC50 of 0.000205 mM in the MTA-13 cell line	11365	
6.3.2.17	5,10-dideaza-5,6,7,8-tetrahydrofolic acid	lometrexo, used to generate the 5,10-dideazatetrahydrofolate resistant cells sublines	11365	
6.3.2.17	5,6,7,8-tetrahydrofolyl-Glu2	60% inhibition of ATP binding at 0.1 mM	118750	
6.3.2.17	5,6,7,8-Tetrahydropteroate	5,6,7,8-tetrahydropteroyl-Glu2 formation	43503	
6.3.2.17	5,6,7,8-Tetrahydropteroyl-Orn	inhibits reaction with 5,6,7,8-tetrahydropteroyl-Glu + ATP and pteroylmonoglutamate + ATP	43505	
6.3.2.17	5,6,7,8-Tetrahydropteroyl-Orn	-	43505	
6.3.2.17	5-fluorouracil	FPGS overexpression significantly enhances chemosensitivity to 5-fluorouracil, FPGS inhibition decreases chemosensitivity to 5-fluorouracil	812	
6.3.2.17	7,8-dihydropteroate	5,6,7,8-tetrahydropteroyl-Glu2 formation	1965	
6.3.2.17	7,8-dihydropteroyl-Glu	5,6,7,8-tetrahydropteroyl-Glu2 formation	5923	
6.3.2.17	adenosine 5'-O-(3-thiotriphosphate)	-	8035	
6.3.2.17	ADP	-	13	
6.3.2.17	ADP	noncompetitive with respect to MgATP2-	13	
6.3.2.17	aminopterin	inhibits reaction with pteroylmonoglutamate + ATP	1003	
6.3.2.17	aminopterin	-	1003	
6.3.2.17	aminopterin	5,6,7,8-tetrahydropteroyl-Glu2 formation	1003	
6.3.2.17	AMP	-	30	
6.3.2.17	ATP4-	-	5937	
6.3.2.17	beta,gamma-Imido-ATP	-	20157	
6.3.2.17	beta,gamma-methylene-ATP	-	3802	
6.3.2.17	Borate	-	1395	
6.3.2.17	dihydrofolate	treatment of cells with trimethoprim leads to inhibition due to accumulation of dihydrofolate through the inhibition of dihydrofolate reductase. Therefore falling dihydrofolate reductase activity leads to falling folylpolyglutamate synthase activity in a domino-like cascade	1351	
6.3.2.17	Dihydropteroic acid	5% inhibition of ATP binding at 0.1 mM	12509	
6.3.2.17	diphosphate	weak, competitive with respect to MgATP2-	17	
6.3.2.17	diphosphate	-	17	
6.3.2.17	Endogenous inhibitor from Neurospora crassa	the inhibitor is present in either polyglutamate-deficient mutants and in wild type. This factor is non-dialyzable, thermolabile and inactivated by urea and trypsin treatment	21009	
6.3.2.17	Folate analogs	-	96506	
6.3.2.17	iodoacetamide	2 mM, 30 to 85% loss of activity in 5 min, depending on the enzyme concentration	67	
6.3.2.17	K+	required at low concentration, inhibition at high concentration	39	
6.3.2.17	L-Glu-gamma-methylester	-	93830	
6.3.2.17	L-Homocysteate	-	16099	
6.3.2.17	L-Homocysteate	prevents or severly retards further addition of Glu	16099	
6.3.2.17	methotrexate	the level required to inhibit the 5,10-dideazatetrahydrofolate resistant cell sublines is unchanged or slightly decreased compared with wild type cells	241	
6.3.2.17	methotrexate	-	241	
6.3.2.17	methotrexate-Glu	IC50 of 0.0000014 mM in the wild type cell line, IC50 of 0.000001 mM to 0.00095 mM in the antifolates-resistant sublines	11364	
6.3.2.17	methotrexate-Glu	IC50 of 0.00002 mM in the wild type cell line, IC50 of 0.0000545 mM in the MTA-13 cell line	11364	
6.3.2.17	methotrexate-phosphinate	competitive inhibition, IC50 of 0.000008 mM, at fixed substrate and recombinant enzyme concentrations. The most potent FPGS inhibitor based on methotrexate heterocycle. CCRF-CEM R2 subline does not respond to inhibition by this compound at 0.001 mM	17306	
6.3.2.17	methotrexate-phosphonate	IC50 0.00012 mM, at fixed substrate and recombinant enzyme concentrations	33881	
6.3.2.17	additional information	no inhibition by methotrexate in the CCRF-CEM R2 cell subline	2	
6.3.2.17	additional information	in Escherichia coli, the addition of L-glutamate to dihydropteroate (dihydrofolate synthetase activity) and the subsequent additions of L-glutamate to tetrahydrofolate (folylpolyglutamate synthetase (FPGS) activity) are catalyzed by the same enzyme, FolC. The presence of a folate binding site in Escherichia coli FolC, which is different from the one seen in folylpolyglutamate synthetases, provides avenues for the design of specific inhibitors of this enzyme in antimicrobial therapy	2	
6.3.2.17	additional information	no substrate: (6R)-5,10-dideaza-5,6,7,8-tetrahydropteroyl-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate-gamma-L-glutamate	2	
6.3.2.17	N-(4-(2(2-amino-3,4-dihydro-4-oxo-7H-pyrolo-(2,3-d)pyrimidine-5-yl)ethyl)-benzoyl)-L-glutamic acid	IC50 of 0.0000136 mM in the wild type cell line, IC50 of 0.000116 mM in the MTA-13 cell line	33880	
6.3.2.17	N-(4-[[(2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl]amino]benzoyl)-L-gamma-glutamyl-5-[(2,4-dicarboxybutyl)(hydroxy)phosphoryl]-L-norvaline	-	78435	
6.3.2.17	N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid	IC50 of 0.0000032 mM in the wild type cell line, IC50 of 0.00032 mM to 0.007168 mM in the antifolates-resistant sublines	13521	
6.3.2.17	N-(5-(N-(3,4-dihydro-2-methyl-4-oxoquinazolin-6-ylmethyl)-N-methylamino)-2-thenoyl)L-glutamic acid	IC50 of 0.0000033 mM in the wild type cell line, IC50 of 0.000028 mM in the MTA-13 cell line	13521	
6.3.2.17	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	13521	
6.3.2.17	Nalpha-(4-amino-4-deoxy-5,8-diazapteroyl)-L-ornithine	-	33887	
6.3.2.17	Nalpha-(4-amino-4-deoxy-5,chloropteroyl)-L-ornithine	-	33890	
6.3.2.17	Nalpha-(4-amino-4-deoxy-8-deazapteroyl)-L-ornithine	-	33888	
6.3.2.17	Nalpha-(4-amino-4-deoxy-N10-methylpteroyl)-Nepsilon-(phosphonoacetyl)-L-lysine	slight inhibition at 0.1 mM	54687	
6.3.2.17	Nalpha-(4-amino-4-deoxypteroyl)-Ndelta-hemiphthaloyl-L-ornithine	IC50 of 0.000001 mM in the wild type cell line, IC50 of 0.000006 mM to 0.0017 mM in the antifolates-resistant sublines	33879	
6.3.2.17	Nalpha-(5,8-dideaza-5-chloropteroyl)-L-ornithine	-	33889	
6.3.2.17	Nalpha-(5,8-dideazapteroyl)-L-ornithine	-	33886	
6.3.2.17	Nalpha-pteroyl-L-ornithine	-	33884	
6.3.2.17	NH4+	required at low concentration, inhibition at high concentration	54	
6.3.2.17	Non-gamma-glutamylatable antifolate analogs	aminopterin analogs are better inhibitors than their methotrexate counterparts	99500	
6.3.2.17	Ornithine-containing folate analogs	e.g. 2,4-diamino-pteroylornithine, 2-amino-4-oxo-5,8-dideazapteroyl-Orn	98522	
6.3.2.17	P1,P5-di(adenosine-5')pentaphosphate	-	2151	
6.3.2.17	pemetrexed	-	1155	
6.3.2.17	pemetrexed disodium	ALIMTA, no inhibition observed with the 5,10-dideazatetrahydrofolate resistant cells sublines	118749	
6.3.2.17	phosphate	-	16	
6.3.2.17	phosphate	competitive with respect to MgATP2-	16	
6.3.2.17	Rb+	required at low concentration, inhibition at high concentration	480	
6.3.2.17	trimethoprim	treatment of cells leads to inhibition due to accumulation of dihydrofolate through the inhibition of dihydrofolate reductase. Therefore falling dihydrofolate reductase activity leads to falling folylpolyglutamate synthase activity in a domino-like cascade	503