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Literature summary extracted from

  • Beierlein, J.M.; Frey, K.M.; Bolstad, D.B.; Pelphrey, P.M.; Joska, T.M.; Smith, A.E.; Priestley, N.D.; Wright, D.L.; Anderson, A.C.
    Synthetic and crystallographic studies of a new inhibitor series targeting Bacillus anthracis dihydrofolate reductase (2008), J. Med. Chem., 51, 7532-7540.
    View publication on PubMedView publication on EuropePMC

Cloned(Commentary)

EC Number Cloned (Comment) Organism
1.5.1.3 expression of His-tagged mutant V77A/I130M/I138V in Escherichia colii strain M15 Bacillus anthracis
1.5.1.3 recombinant expression of the enzyme Homo sapiens

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.1.3 purified recombinant mutant V77A/I130M/I138V enzyme in complex with inhibitor 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine, hanging-drop vapor diffusion in 25% w/v PEG 10,000, 0.1 M MES, pH 6.5, at an equal ratio of protein to crystallization solution. Microseeding is used to obtain isolated crystals in 10% w/v PEG 10000 and 0.1 M MES, pH 6.5, at a protein concentration of 10 mg/ml, improved by 15% ethylene glycol. X-ray diffraction structure determination and analysis at 2.5 A resolution Bacillus anthracis

Protein Variants

EC Number Protein Variants Comment Organism
1.5.1.3 V77A/I130M/I138V site-directed mutagenesis Bacillus anthracis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 2,4-diamino-5-(3-phenylprop-1-ynyl)-6-ethylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-(3-phenylprop-1-ynyl)-6-ethylpyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(2,3-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(2,3-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-methylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-methylpyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-npropylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-npropylpyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]pyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]pyrimidine
-
Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Bacillus anthracis
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
Homo sapiens
1.5.1.3 methotrexate
-
Bacillus anthracis
1.5.1.3 methotrexate
-
Homo sapiens
1.5.1.3 additional information inhibitor design based on a trimethoprim-like scaffold, overview Bacillus anthracis
1.5.1.3 additional information inhibitor design based on a trimethoprim-like scaffold, overview Homo sapiens
1.5.1.3 trimethoprim
-
Bacillus anthracis
1.5.1.3 trimethoprim
-
Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Homo sapiens
-
5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Bacillus anthracis
-
5,6,7,8-tetrahydrofolate + NADP+
-
?

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Bacillus anthracis Q81R22
-
-
1.5.1.3 Homo sapiens
-
-
-

Purification (Commentary)

EC Number Purification (Comment) Organism
1.5.1.3 recombinant enzyme Homo sapiens
1.5.1.3 recombinant His-tagged mutant V77A/I130M/I138V from Escherichia colii strain M15 by nickel affinity chromatography Bacillus anthracis

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
1.5.1.3 7,8-dihydrofolate + NADPH + H+
-
Homo sapiens 5,6,7,8-tetrahydrofolate + NADP+
-
?
1.5.1.3 7,8-dihydrofolate + NADPH + H+
-
Bacillus anthracis 5,6,7,8-tetrahydrofolate + NADP+
-
?

Synonyms

EC Number Synonyms Comment Organism
1.5.1.3 DHFR
-
Homo sapiens
1.5.1.3 DHFR
-
Bacillus anthracis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
1.5.1.3 25
-
assay at Homo sapiens
1.5.1.3 25
-
assay at Bacillus anthracis

pH Optimum

EC Number pH Optimum Minimum pH Optimum Maximum Comment Organism
1.5.1.3 7
-
assay at Homo sapiens
1.5.1.3 7
-
assay at Bacillus anthracis

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADPH
-
Homo sapiens
1.5.1.3 NADPH
-
Bacillus anthracis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.5.1.3 0.000057
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.00013
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(2,3-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.00036
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-(3-phenylprop-1-ynyl)-6-ethylpyrimidine
1.5.1.3 0.00089
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.00094
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.00118
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-npropylpyrimidine
1.5.1.3 0.00128
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.0013
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0013
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0017
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]pyrimidine
1.5.1.3 0.0032
-
pH 7.0, 25°C Homo sapiens 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]pyrimidine
1.5.1.3 0.0032
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-(3-phenylprop-1-ynyl)-6-ethylpyrimidine
1.5.1.3 0.0055
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(2,5-dimethoxyphenyl)prop-1-ynyl]-6-npropylpyrimidine
1.5.1.3 0.0092
-
pH 7.0, 25°C Bacillus anthracis 2,4-diamino-5-[3-(2,3-dimethoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
1.5.1.3 0.071
-
pH 7.0, 25°C Bacillus anthracis trimethoprim
1.5.1.3 0.12
-
pH 7.0, 25°C Homo sapiens trimethoprim