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Literature summary for 1.5.1.3 extracted from

  • Beierlein, J.M.; Karri, N.G.; Anderson, A.C.
    Targeted mutations of Bacillus anthracis dihydrofolate reductase condense complex structure-activity relationships (2010), J. Med. Chem., 53, 7327-7336.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 1.5.1.3

Cloned(Commentary)

Cloned (Comment) Organism
-
 Bacillus anthracis

Crystallization (Commentary)

Crystallization (Comment) Organism
wild type and mutant enzymes bound to trimethoprim and propargyl-linked inhibitors, hanging drop vapor diffusion method, using 22.5% (w/v) PEG 10000, 0.1 M MES, pH 6.75. Microseeding is used to obtain isolated crystals in 12% (w/v) PEG 10000 and 0.1 MES, pH 6.7 Bacillus anthracis

Protein Variants

Protein Variants Comment Organism
F96I the mutant shows strongly reduced catalytic efficiency compared to the wild type enzyme Bacillus anthracis
Y102F the mutant shows reduced catalytic efficiency compared to the wild type enzyme. The affinities of the antifolates increase up to 60fold with this mutant Bacillus anthracis

Inhibitors

Inhibitors Comment Organism Structure
2,4-diamino-5-[3-(2-methoxy-5-phenylphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
 Bacillus anthracis
2,4-diamino-5-[3-(2-phenyl-5-methoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine
-
 Bacillus anthracis
3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol
-
 Bacillus anthracis
5-[3-(2,5-dimethoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(2-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(3-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-(biphenyl-3-yl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine
-
 Bacillus anthracis
5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Bacillus anthracis
6-ethyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
6-ethyl-5-[3-(4-methoxybiphenyl-3-yl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
6-methyl-5-[3-(3,4,5-trimethoxyphenyl)pent-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
6-methyl-5-[3-methyl-3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Bacillus anthracis
trimethoprim
-
 Bacillus anthracis

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
0.01444
-
 7,8-dihydrofolate mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.0337
-
 7,8-dihydrofolate wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.2301
-
 7,8-dihydrofolate mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis

Natural Substrates/ Products (Substrates)

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

Organism

Organism UniProt Comment Textmining
Bacillus anthracis Q81R22
-
-

Purification (Commentary)

Purification (Comment) Organism
nickel affinity column chromatography Bacillus anthracis

Substrates and Products (Substrate)

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

Synonyms

Synonyms Comment Organism
DHFR
-
 Bacillus anthracis

Turnover Number [1/s]

Turnover Number Minimum [1/s] Turnover Number Maximum [1/s] Substrate Comment Organism Structure
1.7
-
 7,8-dihydrofolate mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
4.8
-
 7,8-dihydrofolate mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
9.3
-
 7,8-dihydrofolate wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis

Cofactor

Cofactor Comment Organism Structure
NADPH
-
 Bacillus anthracis

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000049
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.000064
-
 6-ethyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.000083
-
 5-[3-(biphenyl-3-yl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.000097
-
 2,4-diamino-5-[3-(2-methoxy-5-phenylphenyl)prop-1-ynyl]-6-ethylpyrimidine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00017
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.0002
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00023
-
 6-ethyl-5-[3-(4-methoxybiphenyl-3-yl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.0003
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00032
-
 6-ethyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00033
-
 2,4-diamino-5-[3-(2-methoxy-5-phenylphenyl)prop-1-ynyl]-6-ethylpyrimidine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00036
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00037
-
 5-[3-(biphenyl-3-yl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00039
-
 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00043
-
 2,4-diamino-5-[3-(2-phenyl-5-methoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00048
-
 trimethoprim mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00049
-
 2,4-diamino-5-[3-(2-methoxy-5-phenylphenyl)prop-1-ynyl]-6-ethylpyrimidine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00069
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00103
-
 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00104
-
 2,4-diamino-5-[3-(2-phenyl-5-methoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0011
-
 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00115
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00119
-
 6-ethyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00119
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)pent-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00121
-
 6-ethyl-5-[3-(4-methoxybiphenyl-3-yl)prop-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00125
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00131
-
 5-[3-(biphenyl-3-yl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0016
-
 5-[3-(2-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00164
-
 5-[3-(3-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.0017
-
 6-ethyl-5-[3-(4-methoxybiphenyl-3-yl)prop-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00183
-
 5-[3-(2,5-dimethoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.002
-
 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00259
-
 2,4-diamino-5-[3-(2-phenyl-5-methoxyphenyl)prop-1-ynyl]-6-ethylpyrimidine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00266
-
 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00294
-
 6-methyl-5-[3-methyl-3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
0.00337
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)pent-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00391
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)pent-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00428
-
 6-methyl-5-[3-methyl-3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00439
-
 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00451
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00481
-
 6-methyl-5-[3-methyl-3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00489
-
 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00516
-
 5-[3-(2,5-dimethoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00583
-
 5-[3-(2-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.00635
-
 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00752
-
 5-[3-(2,5-dimethoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0092
-
 5-[3-(2-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.00981
-
 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.0102
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.0104
-
 5-[3-(3-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0117
-
 5-[3-(3-methoxybiphenyl-4-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.0137
-
 trimethoprim mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0205
-
 5-[3-(2,5-dimethoxyphenyl)prop-1-yn-1-yl]-6-ethylpyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
0.0241
-
 trimethoprim wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis
0.0341
-
 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis

kcat/KM [mM/s]

kcat/KM Value [1/mMs-1] kcat/KM Value Maximum [1/mMs-1] Substrate Comment Organism Structure
20
-
 7,8-dihydrofolate mutant enzyme F96I, at pH 7.0 and 25°C Bacillus anthracis
120
-
 7,8-dihydrofolate mutant enzyme Y102F, at pH 7.0 and 25°C Bacillus anthracis
280
-
 7,8-dihydrofolate wild type enzyme, at pH 7.0 and 25°C Bacillus anthracis