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Literature summary for 4.6.1.12 extracted from

  • Ramsden, N.L.; Buetow, L.; Dawson, A.; Kemp, L.A.; Ulaganathan, V.; Brenk, R.; Klebe, G.; Hunter, W.N.
    A structure-based approach to ligand discovery for 2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase: a target for antimicrobial therapy (2009), J. Med. Chem., 52, 2531-2542.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 4.6.1.12

Application

Application Comment Organism
drug development framework for the development of IspF inhibitors to generate lead compounds of therapeutic potential against microbial pathogens Escherichia coli

Cloned(Commentary)

Cloned (Comment) Organism
expressed in Escherichia coli strain BL21 (DE3) Escherichia coli

Crystallization (Commentary)

Crystallization (Comment) Organism
IspF-CDP complex, to 1.8 A resolution. IspF in complex with compound 6b, to 3.1 A resolution, belongs to space group I213 with unit cell parameter a = 144 A. IspF in complex with compound 7, to 2.7 A resolution, belongs to space group I213 with unit cell parameter a = 144.5 A. IspF in complex with cytosine arabinoside monophosphate, to 2.1 A resolution, belongs to space group P21 with unit cell parameters a = 88.8 A, b = 54.2 A, c = 118.4 A, beta = 95°. IspF in complex with 5-fluorocytidine, to 2.5 A resolution, belongs to space group C2 with unit cell parameters a = 104.68 A, b = 54.83 A, c = 88.51 A, beta = 99.66°. IspF in complex with cidofovir, to 2.8 A resolution, belongs to space group I213 with unit cell parameter a = 145.68 A Escherichia coli

Inhibitors

Inhibitors Comment Organism Structure
2-amino-N-hydroxy-3-(1-H-indol-3-yl)-propionimidic acid highest affinity of all the ligands examined, due to Zn2+-hydroxamate coordination, KD value of 0.0019 mM Escherichia coli
4-amino-1-(3-O-phosphono-a-D-lyxofuranosyl)pyrimidin-2(1H)-one
-
 Escherichia coli
4-amino-1-[(2S,3aS,4S,6R,6aR)-2-hydroxy-6-(hydroxymethyl)-2-oxidotetrahydrofuro[3,4-d][1,3,2]dioxaphosphol-4-yl]pyrimidin-2(1H)-one KD value of 20.5 mM Escherichia coli
4-amino-1-[(4aR,6R,7R,7aS)-2,7-dihydroxy-2-oxidotetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]pyrimidin-2(1H)-one KD value of 0.925 mM Escherichia coli
5-fluorocytidine KD value of 2.02 mM Escherichia coli
Cidofovir KD value of ca. 40 mM Escherichia coli
Cytosine arabinoside monophosphate KD value of 18.91 mM Escherichia coli
additional information 5-(1,3-benzodioxol-5-ylamino)-5-oxopentanoic acid, 2-[(2,6-diaminopyrimidin-4-yl)sulfanyl]acetamide and 4-(5-amino-1,3,4-oxadiazol-2-yl)-1,2,5-oxadiazol-3-amine are inactive. Activity with compounds 2-amino-N-hydroxy-acetimidic acid, N-hydroxy-nicotinimidic acid, 5-bromo-thiophene-2-sulfonic acid amide, 4-bromobenzenesulfonamide and 4-(4-dimethylamino-phenylazo)-benzenesulfonamide are not measurable Escherichia coli

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis Escherichia coli
Mn2+ Mg2+ or Mn2+, positioned between the alpha- and beta-phosphates of the substrate, acts in concert with the Zn2+ to align and polarize the substrate for catalysis Escherichia coli
Zn2+ Zn2+-binding site, addition of a Zn2+-binding moiety may prove valuable in assisting the design of potent and selective inhibitors Escherichia coli

Organism

Organism UniProt Comment Textmining
Escherichia coli P62617
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-

Purification (Commentary)

Purification (Comment) Organism
-
 Escherichia coli

Synonyms

Synonyms Comment Organism
2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase
-
 Escherichia coli
IspF
-
 Escherichia coli