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Literature summary for 1.5.1.3 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
Search for more literature for 1.5.1.3

Cloned(Commentary)

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

Crystallization (Commentary)

Crystallization (Comment) Organism
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

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

Inhibitors

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

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Bacillus anthracis Q81R22
-
-
Homo sapiens
-
-
-

Purification (Commentary)

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

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
DHFR
-
 Homo sapiens
DHFR
-
 Bacillus anthracis

Temperature Optimum [°C]

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

pH Optimum

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

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Homo sapiens
NADPH
-
 Bacillus anthracis

IC50 Value

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