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Literature summary extracted from

  • Liu, J.; Bolstad, D.B.; Smith, A.E.; Priestley, N.D.; Wright, D.L.; Anderson, A.C.
    Probing the active site of Candida glabrata dihydrofolate reductase with high resolution crystal structures and the synthesis of new inhibitors (2009), Chem. Biol. Drug Des., 73, 62-74.
    View publication on PubMed

Application

EC Number Application Comment Organism
1.5.1.3 drug development the essential enzyme is a target for development of specific inhibitors Nakaseomyces glabratus

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.1.3 purified recombinant enzyme, hanging drop vapor diffusion method, 13 mg/ml protein in 20 mM Tris pH 8.0, 20% glycerol, 0.1 mM EDTA and 2 mM DTT, incubation with 1.5 mM NADPH, mixing with an equal volume of crystallization solution containing 0.1 M Tris, pH 8.5, 35-40% PEG 4000 and 0.3-0.4 M MgCl2, X-ray diffraction structure determination and analysis at 1.95-2.11 A resolution Nakaseomyces glabratus

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)-3-methylbut-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)-3-methylbut-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)pent-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)pent-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(3,5-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(3,5-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(4-methoxyphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(4-methoxyphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(4-tertbutylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(4-tertbutylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(6-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Homo sapiens
1.5.1.3 2,4-diamino-5-[3-(3-methoxy-5-(6-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
-
 Nakaseomyces glabratus
1.5.1.3 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol
-
 Homo sapiens
1.5.1.3 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol
-
 Nakaseomyces glabratus
1.5.1.3 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Homo sapiens
1.5.1.3 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Nakaseomyces glabratus
1.5.1.3 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Homo sapiens
1.5.1.3 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
-
 Nakaseomyces glabratus
1.5.1.3 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Homo sapiens
1.5.1.3 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Nakaseomyces glabratus
1.5.1.3 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Homo sapiens
1.5.1.3 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
-
 Nakaseomyces glabratus
1.5.1.3 additional information inhibitor design, structure-activity relationships of the antifolates: methyl groups at the meta and para positions of the distal phenyl ring achieve the greatest number of interactions with the pathogenic enzyme and the greatest degree of selectivity over the human enzyme, antifungal activity can be tuned with substitution patterns at the propargyl and para-phenyl positions, overview Nakaseomyces glabratus

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+ Nakaseomyces glabratus
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 ?
1.5.1.3 7,8-dihydrofolate + NADPH + H+ Homo sapiens
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 ?

Organism

EC Number Organism UniProt Comment Textmining
1.5.1.3 Homo sapiens
-
-
-
1.5.1.3 Nakaseomyces glabratus Q6FPH0
-
-

Substrates and Products (Substrate)

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

Synonyms

EC Number Synonyms Comment Organism
1.5.1.3 DHFR
-
 Nakaseomyces glabratus
1.5.1.3 DHFR
-
 Homo sapiens

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADPH
-
 Nakaseomyces glabratus
1.5.1.3 NADPH
-
 Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.5.1.3 0.00000055
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00000061
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(3,5-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0000055
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0000064
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(4-methoxyphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0000073
-
-
 Nakaseomyces glabratus 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
1.5.1.3 0.0000073
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(6-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00001
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3-methoxy-5-(4-tertbutylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.000011
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)pent-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.000017
-
-
 Nakaseomyces glabratus 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
1.5.1.3 0.000025
-
-
 Nakaseomyces glabratus 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
1.5.1.3 0.000027
-
-
 Nakaseomyces glabratus 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)-3-methylbut-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00003
-
-
 Nakaseomyces glabratus 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
1.5.1.3 0.000039
-
-
 Nakaseomyces glabratus 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol
1.5.1.3 0.00018
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(4-methoxyphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0002
-
-
 Homo sapiens 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)-3-methylbut-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00021
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(4-tertbutylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00029
-
-
 Homo sapiens 2,4-diamino-5-[3-(3,4,5-trimethoxyphenyl)pent-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0004
-
-
 Homo sapiens 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]pyrimidine-2,4-diamine
1.5.1.3 0.00075
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(2-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00122
-
-
 Homo sapiens 5-[3-methoxy-3-(3,4,5-trimethoxyphenyl)prop-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
1.5.1.3 0.0013
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(2,6-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.00138
-
-
 Homo sapiens 6-methyl-5-[3-(3,4,5-trimethoxyphenyl)but-1-yn-1-yl]pyrimidine-2,4-diamine
1.5.1.3 0.0014
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(3,5-dimethylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0014
-
-
 Homo sapiens 2,4-diamino-5-[3-(3-methoxy-5-(6-methylphenyl)phenyl)but-1-ynyl]-6-methylpyrimidine
1.5.1.3 0.0017
-
-
 Homo sapiens 5-[3-(5-methoxybiphenyl-3-yl)but-1-yn-1-yl]-6-methylpyrimidine-2,4-diamine
1.5.1.3 0.00571
-
-
 Homo sapiens 3-(2,4-diamino-6-methylpyrimidin-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol