Literature summary for 1.5.1.3 extracted from

Cody, V.; Pace, J.; Queener, S.; Adair, O.; Gangjee, A.
Kinetic and structural analysis for potent antifolate inhibition of Pneumocystis jirovecii, Pneumocystis carinii, and human dihydrofolate reductases and their active-site variants (2013), Antimicrob. Agents Chemother., 57, 2669-2677 .

Cloned(Commentary)

Cloned (Comment)	Organism
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli Rosetta Gami B (DE3)	Homo sapiens
recombinant expression of His-tagged wild-type and mutant enzymes in Escherichia coli Rosetta Gami B (DE3)	Pneumocystis carinii
recombinant expression of His-tagged wild-type enzyme in Escherichia coli Rosetta Gami B (DE3)	Pneumocystis jirovecii

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified recombinant detagged wild-type enzyme and mutant K37Q in complex with inhibitor 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine, hanging drop vapour diffusion method, mixing of 20.4 mg/ml protein in 20 mM MES, pH 6.0, 100 mM KCl with a 0:1 molar excess of NADPH and inhibitor, and with reservoir solution containing 100 mM K2HPO4, pH 6.9, 60-64% saturated (NH4)2SO4, and 3% (v/v) ethyl alcohol, 0.01 ml drops, 4°C, for mutant K37Q/F69N, 10.9 mg/ml protein in 10 mM MES, pH 6.0, and 100 mM KCl, is mixed with with a 0:1 molar excess of NADPH and inhibitor, and with a reservoir solution containing 33-36% PEG 2000, 50 mM MES, pH 6.0, and 100 mM KCl, 14°C, X-ray diffraction structure determination and analysis at 2.2 A resolution, modeling	Pneumocystis carinii
purified recombinant detagged wild-type enzyme and mutants Q35K and Q35K/N64F in complex with inhibitor 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine, hanging drop vapour diffusion method, mixing of 6.6-9.8 mg/ml protein in 100 mM K2HPO4, pH 6.9, and 30% saturated (NH4)2SO4 with a 0:1 molar excess of NADPH and inhibitor, and with reservoir solution containing 100 mM K2HPO4, pH 6.9, 60-64% saturated (NH4)2SO4, and 3% v/v ethyl alcohol, 0.01 ml drops, 14°C X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement methods using the coordinates for human DHFR, PDB ID 1U72, modeling	Homo sapiens

Crystallization (Comment)

Organism

purified recombinant detagged wild-type enzyme and mutant K37Q in complex with inhibitor 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine, hanging drop vapour diffusion method, mixing of 20.4 mg/ml protein in 20 mM MES, pH 6.0, 100 mM KCl with a 0:1 molar excess of NADPH and inhibitor, and with reservoir solution containing 100 mM K2HPO4, pH 6.9, 60-64% saturated (NH4)2SO4, and 3% (v/v) ethyl alcohol, 0.01 ml drops, 4°C, for mutant K37Q/F69N, 10.9 mg/ml protein in 10 mM MES, pH 6.0, and 100 mM KCl, is mixed with with a 0:1 molar excess of NADPH and inhibitor, and with a reservoir solution containing 33-36% PEG 2000, 50 mM MES, pH 6.0, and 100 mM KCl, 14°C, X-ray diffraction structure determination and analysis at 2.2 A resolution, modeling

Pneumocystis carinii

purified recombinant detagged wild-type enzyme and mutants Q35K and Q35K/N64F in complex with inhibitor 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine, hanging drop vapour diffusion method, mixing of 6.6-9.8 mg/ml protein in 100 mM K2HPO4, pH 6.9, and 30% saturated (NH4)2SO4 with a 0:1 molar excess of NADPH and inhibitor, and with reservoir solution containing 100 mM K2HPO4, pH 6.9, 60-64% saturated (NH4)2SO4, and 3% v/v ethyl alcohol, 0.01 ml drops, 14°C X-ray diffraction structure determination and analysis at 2.2 A resolution, molecular replacement methods using the coordinates for human DHFR, PDB ID 1U72, modeling

Homo sapiens

Protein Variants

Protein Variants	Comment	Organism
F69F	site-directed mutagenesis	Pneumocystis jirovecii
F69N	site-directed mutagenesis	Pneumocystis jirovecii
F69S	site-directed mutagenesis	Pneumocystis carinii
K37Q	site-directed mutagenesis, the mutant exhibits increased sensitivity for inhibition by 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine compared to the wild-type enzyme	Pneumocystis carinii
K37Q/F69N	site-directed mutagenesis, the mutant exhibits increased sensitivity for inhibition by 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine compared to the wild-type enzyme. Structure analysis of the mutant in complex with TMP, overview	Pneumocystis carinii
K37Q/F69S	site-directed mutagenesis	Pneumocystis carinii
K37S	site-directed mutagenesis	Pneumocystis carinii
K37S/F69N	site-directed mutagenesis	Pneumocystis carinii
K37S/F69S	site-directed mutagenesis	Pneumocystis carinii
N64F	site-directed mutagenesis, the mutant exhibits increased sensitivity for inhibition by 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine compared to the wild-type enzyme	Homo sapiens
N64S	site-directed mutagenesis	Homo sapiens
Q35K	site-directed mutagenesis	Homo sapiens
Q35K/N64F	site-directed mutagenesis	Homo sapiens
Q35K/N64S	site-directed mutagenesis	Homo sapiens
Q35S	site-directed mutagenesis	Homo sapiens
Q35S/N64F	site-directed mutagenesis	Homo sapiens
Q35S/N64S	site-directed mutagenesis	Homo sapiens
S37K	site-directed mutagenesis	Pneumocystis jirovecii
S37K/S69F	site-directed mutagenesis	Pneumocystis jirovecii
S37K/S69N	site-directed mutagenesis	Pneumocystis jirovecii
S37Q/S69F	site-directed mutagenesis	Pneumocystis jirovecii
S37Q/S69N	site-directed mutagenesis	Pneumocystis jirovecii
S73Q	site-directed mutagenesis	Pneumocystis jirovecii

Inhibitors

Inhibitors	Comment	Organism
2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	OAAG324, a potent inhibitor of dihydrofolate reductase, analysis of the enzyme-inhibitor structure of wild-type enzyme and mutants	Homo sapiens
2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	OAAG324, a potent inhibitor of dihydrofolate reductase	Pneumocystis carinii
2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	OAAG324, a potent inhibitor of dihydrofolate reductase	Pneumocystis jirovecii
2,4-diamino-6-[(3',4',5'-trichloroanilino)methyl]pyrido[2,3-d]pyrimidine	-	Homo sapiens
2,4-diamino-6-[(3',4',5'-trichloroanilino)methyl]pyrido[2,3-d]pyrimidine	-	Pneumocystis carinii
2,4-diamino-6-[(3',4',5'-trichloroanilino)methyl]pyrido[2,3-d]pyrimidine	-	Pneumocystis jirovecii
dihydrofolic acid	-	Pneumocystis carinii
methotrexate	-	Homo sapiens
methotrexate	-	Pneumocystis carinii
methotrexate	-	Pneumocystis jirovecii
TMP	structure and ligand binding conformation of TMP	Homo sapiens
TMP	structure and ligand binding conformation of TMP	Pneumocystis carinii
TMP	structure and ligand binding conformation of TMP	Pneumocystis jirovecii
trimethoprim	-	Homo sapiens
trimethoprim	-	Pneumocystis carinii
trimethoprim	-	Pneumocystis jirovecii

KM Value [mM]

KM Value [mM]	KM Value Maximum [mM]	Substrate	Comment	Organism
additional information	-	additional information	Michaelis-Menten steady-state kinetics	Homo sapiens
additional information	-	additional information	Michaelis-Menten steady-state kinetics	Pneumocystis carinii
additional information	-	additional information	Michaelis-Menten steady-state kinetics	Pneumocystis jirovecii
0.0004	-	7,8-dihydrofolate	recombinant mutant Q35K/N64F, pH 7.4, 37°C	Homo sapiens
0.0004	-	7,8-dihydrofolate	recombinant mutant Q35S/N64S, pH 7.4, 37°C	Homo sapiens
0.0005	-	7,8-dihydrofolate	recombinant mutant Q35K, pH 7.4, 37°C	Homo sapiens
0.0007	-	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Homo sapiens
0.0007	-	7,8-dihydrofolate	recombinant mutant Q35K/N64S, pH 7.4, 37°C	Homo sapiens
0.0007	-	7,8-dihydrofolate	recombinant mutant Q35S, pH 7.4, 37°C	Homo sapiens
0.0007	-	7,8-dihydrofolate	recombinant mutant Q35S/N64F, pH 7.4, 37°C	Homo sapiens
0.0008	-	7,8-dihydrofolate	recombinant mutant N64F, pH 7.4, 37°C	Homo sapiens
0.0009	-	7,8-dihydrofolate	recombinant mutant N64S, pH 7.4, 37°C	Homo sapiens
0.002	-	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
0.0024	-	7,8-dihydrofolate	recombinant mutant S37K/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
0.003	-	7,8-dihydrofolate	recombinant mutant S37Q/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0032	-	7,8-dihydrofolate	recombinant mutant S37K/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0034	-	7,8-dihydrofolate	recombinant mutant S69N, pH 7.4, 37°C	Pneumocystis jirovecii
0.0035	-	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis carinii
0.0035	-	7,8-dihydrofolate	recombinant mutant S37Q, pH 7.4, 37°C	Pneumocystis jirovecii
0.0038	-	NADPH	recombinant mutant Q35S, pH 7.4, 37°C	Homo sapiens
0.0038	-	7,8-dihydrofolate	recombinant mutant S37Q/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
0.0045	-	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Homo sapiens
0.0048	-	7,8-dihydrofolate	recombinant mutant S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0053	-	NADPH	recombinant mutant Q35S/N64S, pH 7.4, 37°C	Homo sapiens
0.0056	-	NADPH	recombinant mutant Q35S/N64F, pH 7.4, 37°C	Homo sapiens
0.0057	-	NADPH	recombinant mutant Q35K/N64F, pH 7.4, 37°C	Homo sapiens
0.0063	-	NADPH	recombinant mutant N64S, pH 7.4, 37°C	Homo sapiens
0.0066	-	7,8-dihydrofolate	recombinant mutant F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0066	-	NADPH	recombinant mutant K37S, pH 7.4, 37°C	Pneumocystis carinii
0.0066	-	NADPH	recombinant mutant Q35K/N64S, pH 7.4, 37°C	Homo sapiens
0.007	-	NADPH	recombinant mutant K37S/F69S, pH 7.4, 37°C	Pneumocystis carinii
0.0071	-	7,8-dihydrofolate	recombinant mutant F69S, pH 7.4, 37°C	Pneumocystis carinii
0.0072	-	NADPH	recombinant mutant K37Q, pH 7.4, 37°C	Pneumocystis carinii
0.0075	-	NADPH	recombinant mutant N64F, pH 7.4, 37°C	Homo sapiens
0.0097	-	7,8-dihydrofolate	recombinant mutant K37S/F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0101	-	7,8-dihydrofolate	recombinant mutant K37S, pH 7.4, 37°C	Pneumocystis carinii
0.0106	-	NADPH	recombinant mutant K37Q/F69S, pH 7.4, 37°C	Pneumocystis carinii
0.0107	-	7,8-dihydrofolate	recombinant mutant K37Q/F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0116	-	7,8-dihydrofolate	recombinant mutant K37S/F69S, pH 7.4, 37°C	Pneumocystis carinii
0.0118	-	NADPH	recombinant mutant S37Q, pH 7.4, 37°C	Pneumocystis jirovecii
0.0125	-	NADPH	recombinant mutant Q35K, pH 7.4, 37°C	Homo sapiens
0.0149	-	NADPH	recombinant mutant S37K/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0162	-	NADPH	recombinant mutant S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0163	-	NADPH	recombinant mutant F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0163	-	NADPH	recombinant mutant K37Q/F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0167	-	NADPH	recombinant mutant K37S/F69N, pH 7.4, 37°C	Pneumocystis carinii
0.0173	-	NADPH	recombinant mutant S37Q/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
0.0185	-	7,8-dihydrofolate	recombinant mutant K37Q/F69S, pH 7.4, 37°C	Pneumocystis carinii
0.0189	-	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
0.0192	-	NADPH	recombinant mutant F69S, pH 7.4, 37°C	Pneumocystis carinii
0.023	-	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis carinii
0.0252	-	NADPH	recombinant mutant S69N, pH 7.4, 37°C	Pneumocystis jirovecii
0.0275	-	NADPH	recombinant mutant S37Q/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
0.0864	-	NADPH	recombinant mutant S37K/S69N, pH 7.4, 37°C	Pneumocystis jirovecii

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.
7,8-dihydrofolate + NADPH + H+	Homo sapiens	-	5,6,7,8-tetrahydrofolate + NADP+	-	r
7,8-dihydrofolate + NADPH + H+	Pneumocystis carinii	-	5,6,7,8-tetrahydrofolate + NADP+	-	r
7,8-dihydrofolate + NADPH + H+	Pneumocystis jirovecii	-	5,6,7,8-tetrahydrofolate + NADP+	-	r

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P00374	-	-
Pneumocystis carinii	P16184	-	-
Pneumocystis jirovecii	Q9UUP5	-	-

Purification (Commentary)

Purification (Comment)	Organism
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli Rosetta Gami B (DE3) by nickel affinity chromatography, and tag cleavage through the SUMO protease Ulp1, followed by another step of nickel affinity chromatography to remove the tag	Homo sapiens
recombinant His-tagged wild-type and mutant enzymes from Escherichia coli Rosetta Gami B (DE3) by nickel affinity chromatography, and tag cleavage through the SUMO protease Ulp1, followed by another step of nickel affinity chromatography to remove the tag	Pneumocystis carinii
recombinant His-tagged wild-type enzyme from Escherichia coli Rosetta Gami B (DE3) by nickel affinity chromatography, and tag cleavage through the SUMO protease Ulp1, followed by another step of nickel affinity chromatography to remove the tag	Pneumocystis jirovecii

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.
7,8-dihydrofolate + NADPH + H+	-	Homo sapiens	5,6,7,8-tetrahydrofolate + NADP+	-	r
7,8-dihydrofolate + NADPH + H+	-	Pneumocystis carinii	5,6,7,8-tetrahydrofolate + NADP+	-	r
7,8-dihydrofolate + NADPH + H+	-	Pneumocystis jirovecii	5,6,7,8-tetrahydrofolate + NADP+	-	r

Synonyms

Synonyms	Comment	Organism
DHFR	-	Homo sapiens
DHFR	-	Pneumocystis carinii
DHFR	-	Pneumocystis jirovecii

Temperature Optimum [°C]

Temperature Optimum [°C]	Temperature Optimum Maximum [°C]	Comment	Organism
37	-	assay at	Homo sapiens
37	-	assay at	Pneumocystis carinii
37	-	assay at	Pneumocystis jirovecii

Turnover Number [1/s]

Turnover Number Minimum [1/s]	Turnover Number Maximum [1/s]	Substrate	Comment	Organism
2	8	NADPH	recombinant mutant N64F, pH 7.4, 37°C	Homo sapiens
2	8	7,8-dihydrofolate	recombinant mutant N64F, pH 7.4, 37°C	Homo sapiens
3	6	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
3	6	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
3	6	NADPH	recombinant mutant N64S, pH 7.4, 37°C	Homo sapiens
3	6	7,8-dihydrofolate	recombinant mutant N64S, pH 7.4, 37°C	Homo sapiens
3	6	NADPH	recombinant mutant Q35K/N64S, pH 7.4, 37°C	Homo sapiens
3	6	7,8-dihydrofolate	recombinant mutant Q35K/N64S, pH 7.4, 37°C	Homo sapiens
21	-	NADPH	recombinant mutant Q35S/N64F, pH 7.4, 37°C	Homo sapiens
21	-	7,8-dihydrofolate	recombinant mutant Q35S/N64F, pH 7.4, 37°C	Homo sapiens
23	-	NADPH	recombinant mutant Q35S/N64S, pH 7.4, 37°C	Homo sapiens
23	-	7,8-dihydrofolate	recombinant mutant Q35S/N64S, pH 7.4, 37°C	Homo sapiens
24	-	NADPH	recombinant mutant Q35S, pH 7.4, 37°C	Homo sapiens
24	-	7,8-dihydrofolate	recombinant mutant Q35S, pH 7.4, 37°C	Homo sapiens
26	-	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Homo sapiens
26	-	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Homo sapiens
26	-	NADPH	recombinant mutant S37Q/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
26	-	7,8-dihydrofolate	recombinant mutant S37Q/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
38	-	NADPH	recombinant mutant K37Q, pH 7.4, 37°C	Pneumocystis carinii
38	-	7,8-dihydrofolate	recombinant mutant K37Q, pH 7.4, 37°C	Pneumocystis carinii
39	-	NADPH	recombinant mutant Q35K, pH 7.4, 37°C	Homo sapiens
39	-	7,8-dihydrofolate	recombinant mutant Q35K, pH 7.4, 37°C	Homo sapiens
43	-	NADPH	recombinant mutant Q35K/N64F, pH 7.4, 37°C	Homo sapiens
43	-	7,8-dihydrofolate	recombinant mutant Q35K/N64F, pH 7.4, 37°C	Homo sapiens
45	-	NADPH	recombinant mutant K37S, pH 7.4, 37°C	Pneumocystis carinii
45	-	7,8-dihydrofolate	recombinant mutant K37S, pH 7.4, 37°C	Pneumocystis carinii
47	-	NADPH	recombinant mutant S69N, pH 7.4, 37°C	Pneumocystis jirovecii
47	-	7,8-dihydrofolate	recombinant mutant S69N, pH 7.4, 37°C	Pneumocystis jirovecii
51	-	NADPH	recombinant mutant S37Q, pH 7.4, 37°C	Pneumocystis jirovecii
51	-	7,8-dihydrofolate	recombinant mutant S37Q, pH 7.4, 37°C	Pneumocystis jirovecii
57	-	NADPH	recombinant mutant S37K/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
57	-	7,8-dihydrofolate	recombinant mutant S37K/S69F, pH 7.4, 37°C	Pneumocystis jirovecii
78	-	NADPH	recombinant mutant S37K/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
78	-	7,8-dihydrofolate	recombinant mutant S37K/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
83	-	NADPH	recombinant mutant S69F, pH 7.4, 37°C	Pneumocystis jirovecii
83	-	7,8-dihydrofolate	recombinant mutant S69F, pH 7.4, 37°C	Pneumocystis jirovecii
95	-	NADPH	recombinant mutant S37Q/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
95	-	7,8-dihydrofolate	recombinant mutant S37Q/S69N, pH 7.4, 37°C	Pneumocystis jirovecii
157	-	NADPH	recombinant mutant K37S/F69S, pH 7.4, 37°C	Pneumocystis carinii
157	-	7,8-dihydrofolate	recombinant mutant K37S/F69S, pH 7.4, 37°C	Pneumocystis carinii
158	-	NADPH	recombinant mutant K37Q/F69S, pH 7.4, 37°C	Pneumocystis carinii
158	-	7,8-dihydrofolate	recombinant mutant K37Q/F69S, pH 7.4, 37°C	Pneumocystis carinii
190	-	NADPH	recombinant mutant K37S/F69N, pH 7.4, 37°C	Pneumocystis carinii
190	-	7,8-dihydrofolate	recombinant mutant K37S/F69N, pH 7.4, 37°C	Pneumocystis carinii
204	-	NADPH	recombinant mutant F69S, pH 7.4, 37°C	Pneumocystis carinii
204	-	7,8-dihydrofolate	recombinant mutant F69S, pH 7.4, 37°C	Pneumocystis carinii
223	-	NADPH	recombinant mutant K37Q/F69N, pH 7.4, 37°C	Pneumocystis carinii
223	-	7,8-dihydrofolate	recombinant mutant K37Q/F69N, pH 7.4, 37°C	Pneumocystis carinii
235	-	NADPH	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis carinii
235	-	7,8-dihydrofolate	recombinant wild-type enzyme, pH 7.4, 37°C	Pneumocystis carinii

pH Optimum

pH Optimum Minimum	pH Optimum Maximum	Comment	Organism
7.4	-	assay at	Homo sapiens
7.4	-	assay at	Pneumocystis carinii
7.4	-	assay at	Pneumocystis jirovecii

Cofactor

Cofactor	Comment	Organism
NADP+	-	Homo sapiens
NADP+	-	Pneumocystis carinii
NADP+	-	Pneumocystis jirovecii
NADPH	-	Homo sapiens
NADPH	-	Pneumocystis carinii
NADPH	-	Pneumocystis jirovecii

Ki Value [mM]

Ki Value [mM]	Ki Value maximum [mM]	Inhibitor	Comment	Organism
additional information	-	additional information	inhibition kinetics of wild-type and mutant enzymes, comparison with the inhibition kinetics of enzymes and enzyme mutants from Homo sapiens and Pneumocystis carinii, overview	Pneumocystis jirovecii
additional information	-	additional information	inhibition kinetics of wild-type and mutant enzymes, comparison with the inhibition kinetics of enzymes and enzyme mutants from Homo sapiens and Pneumocystis jirovecii, overview	Pneumocystis carinii
additional information	-	additional information	inhibition kinetics of wild-type and mutant enzymes, comparison with the inhibition kinetics of enzymes and enzyme mutants from Pneumocystis carinii and Pneumocystis jirovecii, overview	Homo sapiens
0.00000026	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	mutant K37Q enzyme, pH 7.4, 37°C	Pneumocystis carinii
0.00000058	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	recombinant mutant N64F enzyme, pH 7.4, 37°C	Homo sapiens
0.00000071	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	mutant K37Q/F69N enzyme, pH 7.4, 37°C	Pneumocystis carinii
0.0000008	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	mutant K37S enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
0.00000142	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	mutant K37S/F69S enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
0.0000027	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	wild-type enzyme, pH 7.4, 37°C	Pneumocystis jirovecii
0.0000063	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	wild-type enzyme, pH 7.4, 37°C	Pneumocystis carinii
0.0000244	-	2,4-diamino-6-[(2',5'-dichloroanilino)methyl]pyrido[2,3-d]pyrimidine	recombinant wild-type enzyme, pH 7.4, 37°C	Homo sapiens

General Information

General Information	Comment	Organism
additional information	homology model of enzyme pjDHFR in ternary complex with NADPH and inhibitor 2,4-diamino-6-[(2',5'-dichloro anilino)methyl]pyrido[2,3-d]pyrimidine	Pneumocystis jirovecii