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Literature summary extracted from

  • Bennett, B.C.; Wan, Q.; Ahmad, M.F.; Langan, P.; Dealwis, C.G.
    X-ray structure of the ternary MTX-NADPH complex of the anthrax dihydrofolate reductase: a pharmacophore for dual-site inhibitor design (2009), J. Struct. Biol., 166, 162-171.
    View publication on PubMedView publication on EuropePMC

Application

EC Number Application Comment Organism
1.5.1.3 drug development DHFR is a valid drug target Bacillus anthracis

Crystallization (Commentary)

EC Number Crystallization (Comment) Organism
1.5.1.3 enzyme in ternary complex with NADPH and inhibitor methotrexate, soaking of crystals in 0.1 M Bis-Tris, pH 5.5, 0.2 M CaCl2 and 22.5% w/v PEG 3350 supplemented with 5 mM beta-NADPH at 4°C for 8 h, cryoprotection with 20% v/v glycerol and 5 mM beta-NADPH, X-ray diffraction structure determination and analysis at 2.3 A resolution Bacillus anthracis

Inhibitors

EC Number Inhibitors Comment Organism Structure
1.5.1.3 2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone) oxime i.e. 373265, a dual-site inhibitor, that targets both the substrate and cofactor binding site, docking modelling, overview Bacillus anthracis
1.5.1.3 6-amino-3-pentadecylphenyl beta-D-glucoside i.e. 1357, a dual-site inhibitor, that targets both the substrate and cofactor binding site Bacillus anthracis
1.5.1.3 methotrexate
-
 Bacillus anthracis
1.5.1.3 additional information the enzyme from Bacillus anthracis is naturally resistant to trimethoprim, at least in part due to the presence of a Phe96 substitution in the putative trimethoprim binding site of the enzyme. Inhibitor development by virtual screening for dual-site inhibitors, overview Bacillus anthracis

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+ Bacillus anthracis
-
 5,6,7,8-tetrahydrofolate + NADP+
-
 ?

Organism

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

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
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
-
 Bacillus anthracis

Temperature Optimum [°C]

EC Number Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
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 7.1
-
 assay at Bacillus anthracis

Cofactor

EC Number Cofactor Comment Organism Structure
1.5.1.3 NADPH binding strutcure and conformation, the adenine moiety adopts an off-plane tilt of nearly 90° and this orientation is stabilized by hydrogen bonds to functionally conserved Arg residues, hydrid transfer and structural role in catalytic mechanism, overview Bacillus anthracis

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
1.5.1.3 0.0165
-
 pH 7.1, 25°C Bacillus anthracis 6-amino-3-pentadecylphenyl beta-D-glucoside
1.5.1.3 0.074
-
 pH 7.1, 25°C Bacillus anthracis 2-(3-(2-(hydroxyimino)-2-(pyridine-4-yl)-6,7-dimethylquinoxalin-2-yl)-1-(pyridine-4-yl)ethanone) oxime

General Information

EC Number General Information Comment Organism
1.5.1.3 physiological function DHFR is essential for the survival and pathogenesis of anthrax. DHFR is required for de novo DNA synthesis and amino acid synthesis Bacillus anthracis