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 (Comment) | Organism |
---|---|
expressed in Escherichia coli strain BL21 (DE3) | Escherichia coli |
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 | 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 | 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 | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | P62617 | - |
- |
Purification (Comment) | Organism |
---|---|
- |
Escherichia coli |
Synonyms | Comment | Organism |
---|---|---|
2C-methyl-D-erythritol-2,4-cyclodiphosphate synthase | - |
Escherichia coli |
IspF | - |
Escherichia coli |