Crystallization (Comment) | Organism |
---|---|
MtDXR in complex with fosmidomycin alone or additionally with inhibitor 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid or inhibitor 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and NADPH, from 25% w/v PEG 3350, 0.2 M ammonium sulfate, and 0.1 M Bis-Tris, pH 5.7-5.9, a cryosolution consists of the screening solution and 25% glycerol, 75 mM NaCl including DMSO, dithiothreitol, cofactors Mn2+ and NADPH, and ligands, i.e. compounds 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid and 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid, X-ray diffraction structure determination and analysis | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid | 92% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid | - |
Mycobacterium tuberculosis | |
3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid | 93% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid | - |
Mycobacterium tuberculosis | |
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate | - |
Mycobacterium tuberculosis | |
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate | - |
Mycobacterium tuberculosis | |
ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate | - |
Mycobacterium tuberculosis | |
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate | - |
Mycobacterium tuberculosis | |
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonate | 20% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
fosmidomycin | - |
Mycobacterium tuberculosis | |
FR900098 | - |
Mycobacterium tuberculosis | |
additional information | design, synthesis, and X-ray crystallographic studies of alpha-aryl 3,4-dichlorophenyl-substituted fosmidomycin analogues as enzyme inhibitors. The introduction of a 3,4-dichlorophenyl group in the Calpha-position relative to the phosphonate group produces analogues that have a higher in vitro antimalarial activity than fosmidomycin | Mycobacterium tuberculosis | |
N-hydroxy-N-[2-(3-hydroxy-3-oxido-3,4-dihydro-1H-2,3-benzoxaphosphinin-4-yl)ethyl]acetamide | 12% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid | 38% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-(2-cyanophenyl)propyl]phosphonic acid | 30% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid | 55% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid | 35% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid | 36% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-[2-(methoxymethyl)phenyl]propyl]phosphonic acid | 30% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonic acid | 20% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-[acetyl(hydroxy)amino]-1-[2-(thiophen-2-yl)phenyl]propyl]phosphonic acid | 30% inhibition at 0.1 mM | Mycobacterium tuberculosis |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | required | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | Mycobacterium tuberculosis | - |
2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | Mycobacterium tuberculosis H37Rv | - |
2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mycobacterium tuberculosis | P9WNS1 | - |
- |
Mycobacterium tuberculosis H37Rv | P9WNS1 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | - |
Mycobacterium tuberculosis | 2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | - |
Mycobacterium tuberculosis H37Rv | 2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
1-deoxy-D-xylulose 5-phosphate reductoisomerase | - |
Mycobacterium tuberculosis |
DXR | - |
Mycobacterium tuberculosis |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
22 | - |
assay at | Mycobacterium tuberculosis |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.5 | - |
assay at | Mycobacterium tuberculosis |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | - |
Mycobacterium tuberculosis |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.00008 | - |
pH 7.5, 22°C | Mycobacterium tuberculosis | fosmidomycin | |
0.00015 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | 3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid | |
0.00016 | - |
pH 7.5, 22°C | Mycobacterium tuberculosis | FR900098 | |
0.0007 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | 3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid | |
0.0056 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | 3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid | |
0.0074 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | (3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid | |
0.022 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate | |
0.038 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate | |
0.1 | - |
above, pH 7,5, 22°C | Mycobacterium tuberculosis | diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate | |
0.1 | - |
above, pH 7,5, 22°C | Mycobacterium tuberculosis | diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate | |
0.15 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | [3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid | |
0.205 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | [3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid | |
0.21 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | [3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid | |
0.465 | - |
pH 7,5, 22°C | Mycobacterium tuberculosis | [3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid |