Application | Comment | Organism |
---|---|---|
drug development | enzyme DXR is an antimicrobial target | Escherichia coli |
drug development | enzyme DXR is an antimicrobial target | Plasmodium falciparum |
drug development | enzyme DXR is an antimicrobial target | Mycobacterium tuberculosis |
Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(2-[[hydroxy(methyl)carbamoyl]oxy]ethyl)phosphonic acid | - |
Escherichia coli | |
(3-acetamidopropyl)phosphonic acid | - |
Escherichia coli | |
(3-boronopropyl)phosphonic acid | MIC90 = 0.053 mg/ml | Escherichia coli | |
(4-hydrazinyl-4-oxobutyl)phosphonic acid | - |
Escherichia coli | |
([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid | - |
Escherichia coli | |
([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid | - |
Plasmodium falciparum | |
([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid | - |
Escherichia coli | |
([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid | - |
Plasmodium falciparum | |
1-hydroxy-5-phenylpyridin-2(1H)-one | - |
Escherichia coli | |
2-[acetyl(hydroxy)amino]ethyl phosphate | - |
Escherichia coli | |
2-[acetyl(hydroxy)amino]ethyl phosphate | - |
Mycobacterium tuberculosis | |
2-[formyl(hydroxy)amino]ethyl phosphate | - |
Escherichia coli | |
2-[formyl(hydroxy)amino]ethyl phosphate | - |
Mycobacterium tuberculosis | |
4-benzylbenzene-1,2-diol | - |
Escherichia coli | |
5-[hydroxy(methyl)amino]-5-oxopentanoic acid | - |
Escherichia coli | |
diethyl (2-[[(furan-2-yl)methyl]amino]-2-oxoethyl)phosphonate | - |
Escherichia coli | |
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate | 43.9% inhibition at 0.25 mM | Escherichia coli | |
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate | 45.2% inhibition at 0.25 mM | Plasmodium falciparum | |
diethyl [2-oxo-2-[(1,3-thiazol-2-yl)amino]ethyl]phosphonate | - |
Escherichia coli | |
diethyl [2-oxo-2-[(pyridin-2-yl)amino]ethyl]phosphonate | - |
Escherichia coli | |
diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate | 40.4% inhibition at 0.25 mM | Escherichia coli | |
diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate | 40.7% inhibition at 0.25 mM | Plasmodium falciparum | |
diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate | 49.2% inhibition at 0.25 mM | Escherichia coli | |
diethyl [3-[3-(hydroxymethyl)anilino]-3-oxopropyl]phosphonate | 17.9% inhibition at 0.25 mM | Escherichia coli | |
fosmidomycin | a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH, strong inhibition | Escherichia coli | |
fosmidomycin | a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH | Mycobacterium tuberculosis | |
fosmidomycin | a natural product, which forms a chelate with the active site divalent metal ion (Mg2+/Mn2+) through its hydroxamate metal-binding group. Competitive versus 1-deoxy-D-xylulose 5-phosphate, uncompetitive versus NADPH. No or poor inhibition by diethyl [3-[3-(hydroxymethyl)anilino]-3-oxopropyl]phosphonate, diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate, and [3-(3-methoxyanilino)-3-oxopropyl]phosphonic acid | Plasmodium falciparum | |
FR-900098 | - |
Escherichia coli | |
FR-900098 | - |
Mycobacterium tuberculosis | |
FR-900098 | - |
Plasmodium falciparum | |
additional information | non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview. No inhibiton at 0.02 mM by [3-(3-methoxyanilino)-3-oxopropyl]phosphonic acid or [3-[benzyl(pyridin-2-yl)amino]-3-oxopropyl]phosphonic acid or [3-[benzyl(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonic acid or [2-[(sulfanylcarbonothioyl)amino]ethyl]phosphonic acid or [3-[(sulfanylcarbonothioyl)amino]propyl]phosphonic acid or [3-(2,3-dihydroxyphenyl)propyl]phosphonic acid | Escherichia coli | |
additional information | non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview | Mycobacterium tuberculosis | |
additional information | non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview | Plasmodium falciparum | |
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | - |
Escherichia coli | |
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | - |
Mycobacterium tuberculosis | |
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | - |
Plasmodium falciparum | |
[(5-phenylpyridin-2-yl)methyl]phosphonic acid | - |
Escherichia coli | |
[(quinolin-2-yl)methyl]phosphonic acid | - |
Escherichia coli | |
[1,1'-biphenyl]-3,4-diol | - |
Escherichia coli | |
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid | - |
Escherichia coli | |
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid | conformation of inhibitor within the MtDXR active site (PDB ID 2Y1D) | Mycobacterium tuberculosis | |
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid | inhibition of strain D2d | Plasmodium falciparum | |
[2-(1-hydroxy-6-oxo-1,6-dihydropyridin-2-yl)ethyl]phosphonic acid | - |
Mycobacterium tuberculosis | |
[2-(2,3-dihydroxyphenyl)ethyl]phosphonic acid | - |
Escherichia coli | |
[2-(3-hydroxy-4-methylphenyl)ethyl]phosphonic acid | - |
Mycobacterium tuberculosis | |
[2-(3-methoxyanilino)-2-oxoethyl]phosphonic acid | 17.8% inhibition at 0.25 mM | Escherichia coli | |
[2-[(hydroxycarbamoyl)oxy]ethyl]phosphonic acid | - |
Escherichia coli | |
[2-[acetyl(hydroxy)amino]ethyl]phosphonic acid | 74% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)propyl]phosphonic acid | MIC90 = 0.063 mg/ml | Escherichia coli | |
[3-oxo-3-[(prop-2-yn-1-yl)amino]propyl]phosphonic acid | 6.7% inhibition at 0.020 mM | Escherichia coli | |
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid | - |
Escherichia coli | |
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid | inhibition of strain D2d | Plasmodium falciparum | |
[4-(2-acetylanilino)-4-oxobutyl]phosphonic acid | - |
Plasmodium falciparum | |
[4-(2-fluoroanilino)-4-oxobutyl]phosphonic acid | - |
Plasmodium falciparum | |
[4-(hydroxyamino)-4-oxobutyl]phosphonic acid | - |
Escherichia coli | |
[4-(methoxyamino)-4-oxobutyl]phosphonic acid | - |
Escherichia coli | |
[4-[2-(methanesulfonyl)anilino]-4-oxobutyl]phosphonic acid | - |
Plasmodium falciparum | |
[4-[acetyl(hydroxy)amino]butyl]phosphonic acid | 80% inhibition at 0.1 mM | Mycobacterium tuberculosis | |
[4-[hydroxy(methyl)amino]-4-oxobutyl]phosphonic acid | - |
Escherichia coli | |
[4-[methoxy(methyl)amino]-4-oxobutyl]phosphonic acid | - |
Escherichia coli | |
[[(isoquinolin-1-yl)amino]methylene]bis(phosphonic acid) | - |
Escherichia coli |
Metals/Ions | Comment | Organism | Structure |
---|---|---|---|
Mg2+ | active site divalent metal ion | Escherichia coli | |
Mg2+ | active site divalent metal ion | Plasmodium falciparum | |
Mg2+ | active site divalent metal ion | Mycobacterium tuberculosis | |
Mn2+ | active site divalent metal ion | Escherichia coli | |
Mn2+ | active site divalent metal ion | Plasmodium falciparum | |
Mn2+ | active site divalent metal ion | Mycobacterium tuberculosis |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | Escherichia coli | - |
2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | Plasmodium falciparum | - |
2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
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+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | Mycobacterium tuberculosis ATCC 25618 | - |
2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Escherichia coli | P45568 | - |
- |
Mycobacterium tuberculosis | P9WNS1 | - |
- |
Mycobacterium tuberculosis ATCC 25618 | P9WNS1 | - |
- |
Mycobacterium tuberculosis H37Rv | P9WNS1 | - |
- |
Plasmodium falciparum | Q8IKG4 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | - |
Escherichia coli | 2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | - |
Plasmodium falciparum | 2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? | |
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+ | - |
? | |
1-deoxy-D-xylulose 5-phosphate + NADPH + H+ | - |
Mycobacterium tuberculosis ATCC 25618 | 2-C-methyl-D-erythritol 4-phosphate + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
1-deoxy-D-xylulose 5-phosphate reductoisomerase | - |
Escherichia coli |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | - |
Plasmodium falciparum |
1-deoxy-D-xylulose 5-phosphate reductoisomerase | - |
Mycobacterium tuberculosis |
DXR | - |
Escherichia coli |
DXR | - |
Plasmodium falciparum |
DXR | - |
Mycobacterium tuberculosis |
EcDXR | - |
Escherichia coli |
MtDXR | - |
Mycobacterium tuberculosis |
PfDXR | - |
Plasmodium falciparum |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADP+ | - |
Escherichia coli | |
NADP+ | - |
Plasmodium falciparum | |
NADP+ | - |
Mycobacterium tuberculosis | |
NADPH | - |
Escherichia coli | |
NADPH | - |
Plasmodium falciparum | |
NADPH | - |
Mycobacterium tuberculosis |
Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
---|---|---|---|---|---|
6.5 | - |
(3-acetamidopropyl)phosphonic acid | pH and temperature not specified in the publication | Escherichia coli |
IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
---|---|---|---|---|---|
0.0000045 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | [(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | |
0.0000059 | - |
pH and temperature not specified in the publication | Escherichia coli | [(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | |
0.000008 | - |
pH and temperature not specified in the publication | Escherichia coli | fosmidomycin | |
0.0000092 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | [(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid | |
0.000018 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | FR-900098 | |
0.000028 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid | |
0.00003 | - |
pH and temperature not specified in the publication | Escherichia coli | FR-900098 | |
0.000036 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | fosmidomycin | |
0.000048 | - |
pH and temperature not specified in the publication | Escherichia coli | [4-[hydroxy(methyl)amino]-4-oxobutyl]phosphonic acid | |
0.000059 | - |
pH and temperature not specified in the publication | Escherichia coli | [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid | |
0.000077 | - |
pH and temperature not specified in the publication | Escherichia coli | 2-[acetyl(hydroxy)amino]ethyl phosphate | |
0.00008 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | fosmidomycin | |
0.000087 | - |
pH and temperature not specified in the publication | Escherichia coli | ([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid | |
0.00009 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid | |
0.000119 | - |
pH and temperature not specified in the publication | Escherichia coli | [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid | |
0.00016 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | FR-900098 | |
0.00017 | - |
pH and temperature not specified in the publication | Escherichia coli | [4-(hydroxyamino)-4-oxobutyl]phosphonic acid | |
0.000279 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | 2-[acetyl(hydroxy)amino]ethyl phosphate | |
0.000342 | - |
pH and temperature not specified in the publication | Escherichia coli | 2-[formyl(hydroxy)amino]ethyl phosphate | |
0.00036 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | ([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid | |
0.00084 | - |
pH and temperature not specified in the publication | Escherichia coli | [(5-phenylpyridin-2-yl)methyl]phosphonic acid | |
0.0011 | - |
pH and temperature not specified in the publication | Escherichia coli | ([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid | |
0.0014 | - |
pH and temperature not specified in the publication | Escherichia coli | 1-hydroxy-5-phenylpyridin-2(1H)-one | |
0.0021 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | 2-[formyl(hydroxy)amino]ethyl phosphate | |
0.003 | - |
above, pH and temperature not specified in the publication | Escherichia coli | (2-[[hydroxy(methyl)carbamoyl]oxy]ethyl)phosphonic acid | |
0.003 | - |
above, pH and temperature not specified in the publication | Escherichia coli | [2-[(hydroxycarbamoyl)oxy]ethyl]phosphonic acid | |
0.004 | - |
pH and temperature not specified in the publication | Escherichia coli | [[(isoquinolin-1-yl)amino]methylene]bis(phosphonic acid) | |
0.0049 | - |
pH and temperature not specified in the publication | Plasmodium falciparum | ([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid | |
0.0159 | - |
pH and temperature not specified in the publication | Escherichia coli | [(quinolin-2-yl)methyl]phosphonic acid | |
0.0224 | - |
pH and temperature not specified in the publication | Escherichia coli | 4-benzylbenzene-1,2-diol | |
0.025 | - |
pH and temperature not specified in the publication | Escherichia coli | 5-[hydroxy(methyl)amino]-5-oxopentanoic acid | |
0.041 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | [2-(3-hydroxy-4-methylphenyl)ethyl]phosphonic acid | |
0.0447 | - |
pH and temperature not specified in the publication | Escherichia coli | [1,1'-biphenyl]-3,4-diol | |
0.053 | - |
pH and temperature not specified in the publication | Mycobacterium tuberculosis | [2-(1-hydroxy-6-oxo-1,6-dihydropyridin-2-yl)ethyl]phosphonic acid | |
0.064 | - |
above, pH and temperature not specified in the publication | Plasmodium falciparum | [4-(2-acetylanilino)-4-oxobutyl]phosphonic acid | |
0.064 | - |
above, pH and temperature not specified in the publication | Plasmodium falciparum | [4-(2-fluoroanilino)-4-oxobutyl]phosphonic acid | |
0.064 | - |
above, pH and temperature not specified in the publication | Plasmodium falciparum | [4-[2-(methanesulfonyl)anilino]-4-oxobutyl]phosphonic acid | |
0.408 | - |
pH and temperature not specified in the publication | Escherichia coli | diethyl (2-[[(furan-2-yl)methyl]amino]-2-oxoethyl)phosphonate | |
0.472 | - |
pH and temperature not specified in the publication | Escherichia coli | diethyl [2-oxo-2-[(pyridin-2-yl)amino]ethyl]phosphonate | |
0.73 | - |
pH and temperature not specified in the publication | Escherichia coli | diethyl [2-oxo-2-[(1,3-thiazol-2-yl)amino]ethyl]phosphonate | |
0.93 | - |
pH and temperature not specified in the publication | Escherichia coli | [4-(methoxyamino)-4-oxobutyl]phosphonic acid | |
1 | - |
pH and temperature not specified in the publication | Escherichia coli | (4-hydrazinyl-4-oxobutyl)phosphonic acid | |
1.2 | - |
pH and temperature not specified in the publication | Escherichia coli | [2-(2,3-dihydroxyphenyl)ethyl]phosphonic acid | |
3.8 | - |
pH and temperature not specified in the publication | Escherichia coli | [4-[methoxy(methyl)amino]-4-oxobutyl]phosphonic acid |
General Information | Comment | Organism |
---|---|---|
malfunction | DXR is essential for the survival of the pathogen, and its inhibition leads to the antimalarial action | Plasmodium falciparum |
malfunction | DXR is essential for the survival of the pathogen, and its inhibition leads to the antitubercular action | Mycobacterium tuberculosis |
metabolism | 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) catalyzes the second step of the nonmevalonate (or MEP) pathway that functions in several organisms and plants for the synthesis of isoprenoids | Escherichia coli |
metabolism | 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) catalyzes the second step of the nonmevalonate (or MEP) pathway that functions in several organisms and plants for the synthesis of isoprenoids | Plasmodium falciparum |
metabolism | 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR) catalyzes the second step of the nonmevalonate (or MEP) pathway that functions in several organisms and plants for the synthesis of isoprenoids | Mycobacterium tuberculosis |
physiological function | DXR is essential for the survival of multiple pathogenic bacteria/parasites | Escherichia coli |
physiological function | DXR is essential for the survival of multiple pathogenic bacteria/parasites, including those that cause tuberculosis and malaria in humans | Plasmodium falciparum |
physiological function | DXR is essential for the survival of multiple pathogenic bacteria/parasites, including those that cause tuberculosis and malaria in humans | Mycobacterium tuberculosis |