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Information on EC 1.1.1.267 - 1-deoxy-D-xylulose-5-phosphate reductoisomerase and Organism(s) Escherichia coli and UniProt Accession P45568
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1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomeraseIUBMB Comments
The enzyme requires Mn2+, Co2+ or Mg2+ for activity, with the first being most effective. The enzyme from several eubacteria, including Escherichia coli, forms part of an alternative nonmevalonate pathway for terpenoid biosynthesis (for diagram, {terp/nonMVA}). The mechanism has been shown to be a retroaldol/aldol reaction .
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Word Map
- 1.1.1.267
-
isoprenoids
- fosmidomycin
- plasmodium
- falciparum
-
antimalarial
-
terpenoids
-
isopentenyl
-
non-mevalonate
- mevalonate
- isoprene
- phosphonate
- drug development
-
dimethylallyl
-
mevalonate-independent
- medicine
- biotechnology
The taxonomic range for the selected organisms is: Escherichia coli
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
1-deoxy-d-xylulose 5-phosphate reductoisomerase, 1-deoxy-d-xylulose-5-phosphate reductoisomerase, 1-deoxy-d-xylulose-5-phosphate, pfdxr, dxp reductoisomerase, mep synthase, cadxr, doxp reductoisomerase, deoxyxylulose 5-phosphate reductoisomerase, mtdxr, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
1-deoxy-D-xylulose 5-phosphate isomeroreductase
-
-
-
-
2-C-methyl-D-erythritol 4-phosphate synthase
deoxyxylulose 5-phosphate reductoisomerase
-
-
-
-
DXP reductoisomerase
-
-
-
-
DXR
2-C-methyl-D-erythritol 4-phosphate synthase
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
mechanism
-
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
stereochemistry
-
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
reaction mechanism
-
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
the reaction does not exhibit burst kinetics for either substrate, indicating that product release is not rate-limiting, the rearrangement step, which precedes hydride transfer, is rate-limiting for 1-deoxy-D-xylulose 5-phosphate but becomes partially ratelimiting for 1-fluoro-1-deoxy-D-xylulose 5-phosphate, thus, rearrangement appears to be enhanced by substitution of a hydrogen atom in the methyl group of 1-deoxy-D-xylulose 5-phosphate by fluorine, consistent with a retro-aldol/aldol mechanism for the rearrangement during conversion of 1-deoxy-D-xylulose 5-phosphate to 2-C-methyl-D-erythritol 4-phosphate
-
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
retro-aldol/aldol mechanism
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
PATHWAY SOURCE
PATHWAYS
BRENDA
-
-, -
SYSTEMATIC NAME
IUBMB Comments
2-C-methyl-D-erythritol-4-phosphate:NADP+ oxidoreductase (isomerizing)
The enzyme requires Mn2+, Co2+ or Mg2+ for activity, with the first being most effective. The enzyme from several eubacteria, including Escherichia coli, forms part of an alternative nonmevalonate pathway for terpenoid biosynthesis (for diagram, {terp/nonMVA}). The mechanism has been shown to be a retroaldol/aldol reaction [2].
CAS REGISTRY NUMBER
COMMENTARY
210756-42-6
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2C-methyl-D-erythritol 4-phosphate + 2C-methyl-D-erythritol 4-phosphate + NADP+
? + NADPH
in reaction mixtures containing 0.15-0.25 mM IspC from Escherichia coli, Mycobacterium tuberculosis or Arabidopsis thaliana, the reversible reaction can be followed over thousands of reaction cycles. No fragment exchange, and the frequency of exchange, if any, is less than 5 p.p.m. per catalytic cycle
-
-
r
2C-methyl-D-erythritol 4-phosphate + hydroxyacetone + NADP+
? + NADPH
reaction mixtures containing 0.23-0.25 mM IspC from Escherichia coli, Mycobacterium tuberculosis or Arabidopsis thaliana
-
-
?
glycolaldehyde phosphate + hydroxyacetone + NADPH
? + NADP+
reaction mixtures containing 0.21-0.34 mM IspC from Escherichia coli, Mycobacterium tuberculosis or Arabidopsis thaliana
-
-
?
1-deoxy-D-xylulose 5-phosphate + NAD(P)H + H+
2-C-methyl-D-erythritol 4-phosphate + NAD(P)+
-
inverse secondary kinetic isotope effects for both 3-[2H] and 4-[2H]-D-1-deoxyxylulose-5-phosphate during DXR-catalyzed isomerization indicates that the enzyme operates through a retro-aldol/aldol mechanism
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
key enzyme in the bacterial nonmevalonate pathway to terpenoids, DXR introduces the key branching structure required for the eventual production of isopentenyl diphosphate
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
involved in the biosynthesis of isopentenylphosphate
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
i.e. DXP
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
i.e. DXP
-
-
r
1-deoxy-D-xylulose-5-phosphate + NADPH
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose-5-phosphate + NADPH
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
r
1-fluoro-1-deoxy-D-xylulose 5-phosphate + NADPH
?
-
i.e. CF-DXP, results in about 25% of the activity with 1-deoxy-D-xylulose 5-phosphate
-
-
r
additional information
?
-
IspC does not catalyze the isomerisation of 1-deoxy-D-xylulose 5-phosphate to give 1-deoxy-L-ribulose 5-phosphate. Active site of IspC is located close to the surface, a flexible loop at the active site (amino acids 206-216) is able to fold into at least three different conformations
-
-
?
additional information
?
-
-
IspC does not catalyze the isomerisation of 1-deoxy-D-xylulose 5-phosphate to give 1-deoxy-L-ribulose 5-phosphate. Active site of IspC is located close to the surface, a flexible loop at the active site (amino acids 206-216) is able to fold into at least three different conformations
-
-
?
additional information
?
-
-
reaction depends on NADPH although it does not involve a reduction step, putative aldehyde intermediate is converted to methyl-D-erythritol-4-phosphate in the presence of NADPH and to 1-deoxy-D-xylolose-5-phosphate in the presence of NADP+
-
-
?
additional information
?
-
-
1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid, 1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid, and 1,2-dideoxy-D-hexulose 6-phosphate are poor substrates
-
-
?
additional information
?
-
C3-C4 substrate binding mode in which DXP chelates a DXR-bound divalent cation via its hydroxyl groups at C3 and C4. The conversion of 1-deoxy-D-xylulose 5-phosphate to 2-methyl-D-erythritol 4-phosphate max include a pseudo-single molecule transition state of the retro-aldol intermediates
-
-
?
additional information
?
-
-
C3-C4 substrate binding mode in which DXP chelates a DXR-bound divalent cation via its hydroxyl groups at C3 and C4. The conversion of 1-deoxy-D-xylulose 5-phosphate to 2-methyl-D-erythritol 4-phosphate max include a pseudo-single molecule transition state of the retro-aldol intermediates
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
key enzyme in the bacterial nonmevalonate pathway to terpenoids, DXR introduces the key branching structure required for the eventual production of isopentenyl diphosphate
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
ir
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
-
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
involved in the biosynthesis of isopentenylphosphate
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mn2+
Mg2+
Mn2+
Mg2+
the enzyme requires the presence of a divalent metal ion for activity
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(3-(hydroxy[(pentafluorophenyl)carbonyl]amino)propyl)phosphonic acid
-
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate
43.9% inhibition at 0.25 mM
diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate
40.4% inhibition at 0.25 mM
-
diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate
49.2% inhibition at 0.25 mM
-
diethyl [3-[3-(hydroxymethyl)anilino]-3-oxopropyl]phosphonate
17.9% inhibition at 0.25 mM
-
epigallocatechin gallate
specifically inhibits the enzyme and has antimicrobial activity, competitive inhibition versus DXP and uncompetitive inhibition versus NADPH
fosmidomycin analogues
synthesis, stereochemistry, and analysis of inhibitory potency of several fosmidomycin analogues, overview
-
theaflavin-3,3'-digallate
strong inhibition of DXR, isolated from Camellia sinenesis
[(1-isoquinolinylamino)methylene]-1,1-bisphosphonate
50% inhibition at 0.004 mM
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid
-
-
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
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[2-(3-methoxyanilino)-2-oxoethyl]phosphonic acid
17.8% inhibition at 0.25 mM
-
[3-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)propyl]phosphonic acid
MIC90 = 0.063 mg/ml
-
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid 3-methylbutyl ester
-
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-1-yl-ethyl) ester
-
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-2-yl-ethyl) ester
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[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono-n-propyl ester
-
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid monophenethyl ester
-
[3-oxo-3-[(prop-2-yn-1-yl)amino]propyl]phosphonic acid
6.7% inhibition at 0.020 mM
-
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid
-
[[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate
50% inhibition at 0.007 mM
(2R,3R)-4-amino-2,3-dihydroxybutyl dihydrogen phosphate
-
very weak inhibitor, IC50: 5 mM, above
(2R,3S)-2,3-dihydroxy-4-(hydroxyamino)-4-oxobutyl dihydrogen phosphate
-
very weak inhibitor, IC50: 5 mM, above
(2R,3S)-4-amino-2,3-dihydroxy-4-oxobutyl dihydrogen phosphate
-
IC50: 0.253 mM
(4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonic acid
-
26.8% inhibition
1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid
-
i.e. CF3-DXP, very low inhibition
1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid
-
i.e. CF2-DXP, very low inhibition
1-hydroxy-5-phenylpyridin-2(1H)-one
-
minimal inhibitory concentration for growth 0.1 mM
2-[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-hydroxyacetamide
inhibitor keeps its inhibition capacity in the presence of Triton X-100 and shows antimicrobial activity against Escherichia coli
3-[(([(3,4-dimethoxyphenyl)acetyl]amino)acetyl)(hydroxy)amino]propylphosphonic acid
-
-
3-[([(cyclopropylcarbonyl)amino]acetyl)(hydroxy)amino]propylphosphonic acid
-
-
3-[hydroxy(([3-(trifluoromethoxy)benzoyl]amino)acetyl)amino]propylphosphonic acid
-
-
3-[hydroxy(([4-(1H-indol-3-yl)butanoyl]amino)acetyl)amino]propylphosphonic acid
-
-
diethyl (2-[[3-(hydroxymethyl)phenyl]amino]-2-oxoethyl)phosphonate
-
40.4% inhibition
diethyl (3-[[3-(hydroxymethyl)phenyl]amino]-3-oxopropyl)phosphonate
-
17.9% inhibition
diethyl [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonate
-
24.4% inhibition
diethyl [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonate
-
33.5% inhibition
diethyl [3-[(3-methoxyphenyl)amino]-3-oxopropyl]phosphonate
-
14.1% inhibition
gallocatechin gallate
-
completely suppresses the activity of DXR at 100 microM, and shows around 50% DXR inhibition at 25 microM
theaflavin-3'-gallate
-
non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH
theaflavin-3,3'-digallate
-
non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH
theaflavin-3-gallate
-
non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH
[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
inhibitor keeps its inhibition capacity in the presence of Triton X-100
fosmidomycin
acts by binding strongly to DXR as a slow tight-binding inhibitor, inhibitor-enzyme interaction and structure analysis for design of inhibitors, possibly mimics a transition state in the reaction coordinate of the substrate, the initial rapid equilibrium is subject to negative cooperativity, overview
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
fosmidomycin
a naturally occurring retrohydroxamate phosphonic acid. DXR-NADPH-fosmidomycin complex crystal structure analysis, the phosphonate group of the inhibitor is located in the phosphate binding cleft of the substrate DXP and is bound in a similar fashion as the phosphate group
gallocatechin gallate
specifically inhibits the enzyme and has antimicrobial activity, competitive inhibition versus DXP and uncompetitive inhibition versus NADPH
gallocatechin gallate
strong inhibition of DXR, isolated from Camellia sinenesis
additional information
neither the sulfone (N-hydroxy-N-[3-(alkylsulfonyl)propyl]acetamides) nor the sulfonamide derivatives (N-hydroxy-N-(3-sulfamoylpropyl) acetamide and N-hydroxy-N-(3-(N-alkylsulfamoyl)propyl)acetamide) of FR900098 display any significant inhibitory activity against DXR at a concentration of 0.03 mM. Importance of the negative charge for the binding of fosmidomycin-like inhibitors to DXR. Uncharged molecules are virtually inactive whereas derivatives that possess only one instead of two negative charges are markedly less active. It is possible to regain some of the activity that is lost by the reduction of the charge by occupation of hitherto unexploited areas of the enzyme
-
additional information
determination of the antimicrobial activities of various essential oils against different microbials using 35 plant essential oils (EOs), which have long been recognized for their antimicrobial properties. Essential oils of Zanbthoxylum bungeanum (ZB), Schizonepetae tenuifoliae (ST), Thymus quinquecostatus (TQ), Origanum vulgare (OV), and Eugenia caryophyllata (EC) display weak to medium inhibitory activity against DXR, with IC50 values of 0.078 mg/ml, 0.065 mg/ml, 0.059 mg/ml, 0.048 mg/ml, and 0.037 mg/ml, respectively. Dry roots or dry fruits are used for extraction. Cercis siliquastrum leaf extract strongly inhibits enzyme DXR. No effect by 0.5% DMSO on enzyme activity
-
additional information
-
determination of the antimicrobial activities of various essential oils against different microbials using 35 plant essential oils (EOs), which have long been recognized for their antimicrobial properties. Essential oils of Zanbthoxylum bungeanum (ZB), Schizonepetae tenuifoliae (ST), Thymus quinquecostatus (TQ), Origanum vulgare (OV), and Eugenia caryophyllata (EC) display weak to medium inhibitory activity against DXR, with IC50 values of 0.078 mg/ml, 0.065 mg/ml, 0.059 mg/ml, 0.048 mg/ml, and 0.037 mg/ml, respectively. Dry roots or dry fruits are used for extraction. Cercis siliquastrum leaf extract strongly inhibits enzyme DXR. No effect by 0.5% DMSO on enzyme activity
-
additional information
hydroxamate analogues of fosfoxacin, the phosphate homologue of fosmidomycin, as inhibitors of DXR, synthesis and activities, analysis of Escherichia coli strain XL-1 Blue cell growth inhibition, overview
-
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
-
additional information
possible interactions between DXR and the catechine inhibitors are simulated via molecular docking simulation, detailed overview. Triton X-100 does not affect the inhibition of the enzyme by epigallocatechin gallate and gallocatechin gallate, but that by baicalein (positive control)
-
additional information
-
1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid, 1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid, and 1,2-dideoxy-D-hexulose 6-phosphate are poor inhibitors, most likely because of the increase in steric bulk at C1
-
additional information
-
inhibitory potencies of a series of aryl- and heteroarylcarbamoylphosphonic acids, their diethyl esters and disodium salts as analogues of the potent DXR inhibitor fosmidomycin, effects of the carboxamide N-substituents and the length of the methylene linker, in silico docking studies, saturation transfer difference NMR spectroscopy and enzyme inhibition assays, overview. Molecular modelling and simulated docking studies. No or poor inhibition by diethyl (4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonate, diethyl [5-[(3-hydroxyphenyl)amino]-5-oxopentyl]phosphonate, [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonic acid, [5-[(3-bromophenyl)amino]-5-oxopentyl]phosphonic acid, diethyl [5-[(3-methoxyphenyl)amino]-5-oxopentyl]phosphonate, [4-[(3-methoxyphenyl)amino]-4-oxobutyl]phosphonic acid, [5-[(3-methoxyphenyl)amino]-5-oxopentyl]phosphonic acid, diethyl [4-[(3-bromophenyl)amino]-4-oxobutyl]phosphonate, [4-[(3-bromophenyl)amino]-4-oxobutyl]phosphonic acid, and [5-[(3-bromophenyl)amino]-5-oxopentyl]phosphonic acid
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.227
1-fluoro-1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
additional information
additional information
-
steady-state and single-turnover kinetics, primary kinetic isotope effects, overview
-
0.081
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant His-tagged enzyme
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
37
1-fluoro-1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
29
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
33
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant His-tagged enzyme
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.5
(3-acetamidopropyl)phosphonic acid
pH and temperature not specified in the publication
-
2
1,1,1-trifluoro-1-deoxy-D-xylulose 5-phosphoric acid
-
pH 7.6, 37°C, recombinant enzyme
3.4
1,1-difluoro-1-deoxy-D-xylulose 5-phosphoric acid
-
pH 7.6, 37°C, recombinant enzyme
0.0014
1-hydroxy-5-phenylpyridin-2(1H)-one
-
pH not specified in the publication, temperature not specified in the publication
0.0224
4-benzylbenzene-1,2-diol
-
pH not specified in the publication, temperature not specified in the publication
0.0447
biphenyl-3,4-diol
-
pH not specified in the publication, temperature not specified in the publication
0.000042
[3-[acetyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd5
0.000082
[3-[acetyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd6
0.00093
[3-[acetyl(hydroxy)amino]-1-phenylpropyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd8
0.000087
[3-[formyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd3
0.000035
[3-[formyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd4
0.0015
[3-[formyl(hydroxy)amino]-1-phenylpropyl]phosphonic acid
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd7
0.1483
epigallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, competitive versus 1-deoxy-D-xylulose 5-phosphate
0.1794
epigallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, uncompetitive versus NADPH
0.0234
gallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, uncompetitive versus NADPH
0.0252
gallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, competitive versus 1-deoxy-D-xylulose 5-phosphate
0.000034
fosmidomycin
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd2
0.0222
theaflavin-3'-gallate
-
substrate 1-deoxy-D-xylulose 5-phosphate, pH 7.4, 37°C
0.0133
theaflavin-3,3'-digallate
-
substrate 1-deoxy-D-xylulose 5-phosphate, pH 7.4, 37°C
0.03
theaflavin-3-gallate
-
substrate 1-deoxy-D-xylulose 5-phosphate , pH 7.4, 37°C
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.003
(2-[[hydroxy(methyl)carbamoyl]oxy]ethyl)phosphonic acid
Escherichia coli
above, pH and temperature not specified in the publication
-
0.0013
(3-(hydroxy[(pentafluorophenyl)carbonyl]amino)propyl)phosphonic acid
Escherichia coli
pH 7.5, 30°C
0.0054
(3-[hydroxy(5-oxohexanoyl)amino]propyl)phosphonic acid
Escherichia coli
pH 7.5, 30°C
0.0051
(3-[hydroxy(6-phenylhexanoyl)amino]propyl)phosphonic acid
Escherichia coli
pH 7.5, 30°C
0.0056
(3-[hydroxy(hexadecanoyl)amino]propyl)phosphonic acid
Escherichia coli
pH 7.5, 30°C
1
(4-hydrazinyl-4-oxobutyl)phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.000087
([[acetyl(hydroxy)amino]methoxy]methyl)phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.0011
([[formyl(hydroxy)amino]methoxy]methyl)phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.0014
1-hydroxy-5-phenylpyridin-2(1H)-one
Escherichia coli
pH and temperature not specified in the publication
0.000077
2-[acetyl(hydroxy)amino]ethyl phosphate
Escherichia coli
pH and temperature not specified in the publication
-
0.000077
2-[acetyl(methyl)amino]ethyl phosphate
Escherichia coli
pH 7.5, 37°C, recombinant His-tagged enzyme
-
0.000342
2-[formyl(hydroxy)amino]ethyl phosphate
Escherichia coli
pH and temperature not specified in the publication
-
0.0026
3-(hydroxyamino)-3-oxopropyl phosphate
Escherichia coli
pH 7.5, 37°C, recombinant His-tagged enzyme
-
0.000046
3-[hydroxy(methyl)amino]-3-oxopropyl phosphate
Escherichia coli
pH 7.5, 37°C, recombinant His-tagged enzyme
-
0.0224
4-benzylbenzene-1,2-diol
Escherichia coli
pH and temperature not specified in the publication
0.025
5-[hydroxy(methyl)amino]-5-oxopentanoic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.408
diethyl (2-[[(furan-2-yl)methyl]amino]-2-oxoethyl)phosphonate
Escherichia coli
pH and temperature not specified in the publication
-
0.73
diethyl [2-oxo-2-[(1,3-thiazol-2-yl)amino]ethyl]phosphonate
Escherichia coli
pH and temperature not specified in the publication
-
0.472
diethyl [2-oxo-2-[(pyridin-2-yl)amino]ethyl]phosphonate
Escherichia coli
pH and temperature not specified in the publication
-
0.00003
FR-900098
Escherichia coli
pH and temperature not specified in the publication
0.0000059
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.00084
[(5-phenylpyridin-2-yl)methyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
0.0159
[(quinolin-2-yl)methyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.0447
[1,1'-biphenyl]-3,4-diol
Escherichia coli
pH and temperature not specified in the publication
-
0.000059
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
1.2
[2-(2,3-dihydroxyphenyl)ethyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.003
[2-[(hydroxycarbamoyl)oxy]ethyl]phosphonic acid
Escherichia coli
above, pH and temperature not specified in the publication
-
0.0021
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid 3-methylbutyl ester
Escherichia coli
at 0.03 mM
0.0024
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-1-yl-ethyl) ester
Escherichia coli
at 0.03 mM
0.0016
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono(2-naphthalen-2-yl-ethyl) ester
Escherichia coli
at 0.03 mM
0.0039
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono-n-butyl ester
Escherichia coli
at 0.03 mM
0.016
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid mono-n-propyl ester
Escherichia coli
at 0.03 mM
0.05
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid monomethyl ester
Escherichia coli
at 0.03 mM
0.00049
[3-(acetyl(hydroxy)amino)propyl]phosphonic acid monophenethyl ester
Escherichia coli
at 0.03 mM
0.023
[3-(acetyl(hydroxy)amino)propyl]phosphonic monoethyl ester
Escherichia coli
at 0.03 mM
0.000119
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
0.93
[4-(methoxyamino)-4-oxobutyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
3.8
[4-[methoxy(methyl)amino]-4-oxobutyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.004
[[(isoquinolin-1-yl)amino]methylene]bis(phosphonic acid)
Escherichia coli
pH and temperature not specified in the publication
-
5
(2R,3R)-4-amino-2,3-dihydroxybutyl dihydrogen phosphate
Escherichia coli
-
very weak inhibitor, IC50: 5 mM, above
5
(2R,3S)-2,3-dihydroxy-4-(hydroxyamino)-4-oxobutyl dihydrogen phosphate
Escherichia coli
-
very weak inhibitor, IC50: 5 mM, above
0.253
(2R,3S)-4-amino-2,3-dihydroxy-4-oxobutyl dihydrogen phosphate
Escherichia coli
-
IC50: 0.253 mM
0.0038 - 0.0061
2-[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-hydroxyacetamide
0.02
3-(hydroxy([(2-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid
Escherichia coli
-
-
0.012
3-(hydroxy([(3-methylbutanoyl)amino]acetyl)amino)propylphosphonic acid
Escherichia coli
-
-
0.001
3-(hydroxy([(4-phenoxybutanoyl)amino]acetyl)amino)propylphosphonic acid
Escherichia coli
-
-
0.019
3-(hydroxy([(4-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid
Escherichia coli
-
-
0.014
3-[(([(3,4-dimethoxyphenyl)acetyl]amino)acetyl)(hydroxy)amino]propylphosphonic acid
Escherichia coli
-
-
0.0071
3-[([(cyclopropylcarbonyl)amino]acetyl)(hydroxy)amino]propylphosphonic acid
Escherichia coli
-
-
0.0051
3-[hydroxy(([3-(trifluoromethoxy)benzoyl]amino)acetyl)amino]propylphosphonic acid
Escherichia coli
-
-
0.017
3-[hydroxy(([4-(1H-indol-3-yl)butanoyl]amino)acetyl)amino]propylphosphonic acid
Escherichia coli
-
-
0.0031 - 0.0044
[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
0.000008
fosmidomycin
Escherichia coli
pH and temperature not specified in the publication
0.00017
[4-(hydroxyamino)-4-oxobutyl]phosphonic acid
Escherichia coli
pH 7.5, 37°C, recombinant His-tagged enzyme
0.00017
[4-(hydroxyamino)-4-oxobutyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
0.000048
[4-[hydroxy(methyl)amino]-4-oxobutyl]phosphonic acid
Escherichia coli
pH 7.5, 37°C, recombinant His-tagged enzyme
-
0.000048
[4-[hydroxy(methyl)amino]-4-oxobutyl]phosphonic acid
Escherichia coli
pH and temperature not specified in the publication
-
0.0038
2-[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-hydroxyacetamide
Escherichia coli
pH 7.5, 37°C
0.0061
2-[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]-N-hydroxyacetamide
Escherichia coli
presence of 0.01% Triton X-100, pH 7.5, 37°C
0.0031
[(5Z)-5-(3,4-dihydroxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl]acetic acid
Escherichia coli
pH 7.5, 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
physiological function
metabolism
metabolism
1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is the first key enzyme in the MEP pathway for terpenoid biosynthesis
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
metabolism
rate-limiting enzyme in the 2-methyl-D-erythritol-4-phosphate (MEP) terpenoid biosynthetic pathway catalyzing the second step
physiological function
DXR is essential for the survival of multiple pathogenic bacteria/parasites
physiological function
in many pathogenic bacteria, the enzymes of the 2-C-methyl-D-erythrirol 4-phosphate (MEP) pathway are involved in the biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate, the two universal and essential units for the biosynthesis of isoprenoids. The enzyme 1-deoxyxylulose 5-phosphate reductoisomerase (DXR) that catalyzes the transformation of 1-deoxy-D-xylulose 5-phosphate (DXP) to 2-C-methyl-D-erythritol 4-phosphate (MEP) via an isomerization and a NADPH-dependent reduction reaction
metabolism
-
the 1-deoxy-D-xylulose-5-phosphate reductoisomerase is the second enzyme in the nonmevalonate isoprene biosynthesis pathway, catalyzing the reductive isomerization of 1-deoxy-D-xylulose-5-phosphate to 2-methyl-D-erythritol-4-phosphate for making isopentenyl diphosphate and dimethylallyl diphosphate
metabolism
-
the enzyme is involved in the isoprenoid biosynthetic DOXP/MEP pathway
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
docking models for inhibitor (3-[hydroxy(5-oxohexanoyl)amino]propyl)phosphonic acid based on crystal structure in complex with fosmidomycin. Formation of a hydrogen bond between an appropriately placed carbonyl group in the acyl residue and the main-chain NH of M214 located in the flexible catalytic loop of the enzyme
in complex with inhibitor [(1-isoquinolinylamino)methylene]-1,1-bisphosphonate and in complex with inhibitor [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate
in complex with Mg2+, NADPH, and inhibitor fosmidomycin. Protein exhibits a well-ordered conformation upon substrate binding. No electron density is observed for the nicotinamide-ribose portion of NADPH and the position of D149 anchoring Mg2+ is shifted by NADPH in the active site
selenomethionine labelled enzyme in ternary complex with the antimalarial compound fosmidomycin and NADPH
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
2-C-methyl-D-erythritol 4-phosphate pathway gene-disrupted Escherichia coli mutants. DXR is functionally active in Escherichia coli mutant DYM1
additional information
-
2-C-methyl-D-erythritol 4-phosphate pathway gene-disrupted Escherichia coli mutants. DXR is functionally active in Escherichia coli mutant DYM1
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
by immobilized metal affinity chromatography on a Co column, followed by anion exchange chromatography, gel filtration and ultrafiltration
-
recombinant His-tagged enzyme by nickkel affinity chromatography and gel filtration
-
recombinant His-tagged enzyme from overexpressing strain BL21 by nickel affinity chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
dxr gene amplified and inserted into the pQE9 expression vector resulting in a protein with an amino-terminal His6-tag
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
drug development
-
Escherichia coli Dxr represents a valuable model enzyme for the screening for new antimalarial compounds, since work with the Plasmodium falciparum Dxr is associated with considerably high effort due to the instability of this enzyme and the low yield of the available recombinant expression system, no major differences in the IC50 between Escherichia coli Dxr and Plasmodium falciparum Dxr
additional information
drug development
the enzyme from Escherichia coli is a valuable target for the development of antimicrobial compounds
additional information
the enzyme is a target for development of antibacterial drugs, determination of the antimicrobial activities of various essential oils against different microbials
additional information
-
the enzyme is a target for development of antibacterial drugs, determination of the antimicrobial activities of various essential oils against different microbials
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Radykewicz, T.; Rohdich, F.; Wungsintaweekul, J.; Herz, S.; Kis, K.; Eisenreich, W.; Bacher, A.; Zenk, M.H.; Arigoni, D.
Biosynthesis of terpenoids: 1-deoxy-D-xylulose-5-phosphate reductoisomerase from Escherichia coli is a class B dehydrogenase
FEBS Lett.
465
157-160
2000
Escherichia coli
Yajima, S.; Nonaka, T.; Kuzuyama, T.; Seto, H.; Ohsawa, K.
Crystal structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase complexed with cofactors: Implications of a flexible loop movement upon substrate binding
J. Biochem.
131
313-317
2002
Escherichia coli
Reuter, K.; Sanderbrand, S.; Jomaa, H.; Wiesner, J.; Steinbrecher, I.; Beck, E.; Hintz, M.; Klebe, G.; Stubbs, M.T.
Crystal structure of 1-deoxy-D-xylulose-5-phosphate reductoisomerase, a crucial enzyme in the non-mevalonate pathway of isoprenoid biosynthesis
J. Biol. Chem.
277
5378-5384
2002
Escherichia coli
Takahashi, S.; Kuzuyama, T.; Watanabe, H.; Seto, H.
A 1-deoxy-D-xylulose 5-phosphate reductoisomerase catalyzing the formation of 2-C-methyl-D-erythritol 4-phosphate in an alternative nonmevalonate pathway for terpenoid biosynthesis
Proc. Natl. Acad. Sci. USA
95
9879-9884
1998
Escherichia coli
Kuzuyama, T.; Takahashi, S.; Takagi, M.; Seto, H.
Characterization of 1-deoxy-D-xylulose 5-phosphate reductoisomerase, an enzyme involved in isopentenyl diphosphate biosynthesis, and identification of its catalytic amino acid residues
J. Biol. Chem.
275
19928-19932
2000
Escherichia coli (P45568), Escherichia coli
Hoeffler, J.F.; Tritsch, D.; Grosdemange-Billiard, C.; Rohmer, M.
Isoprenoid biosynthesis via the methylerythritol phosphate pathway. Mechanistic investigations of the 1-deoxy-D-xylulose 5-phosphate reductoisomerase
Eur. J. Biochem.
269
4446-4457
2002
Escherichia coli
Yajima, S.; Hara, K.; Sanders, J.M.; Yin, F.; Ohsawa, K.; Wiesner, J.; Jomaa, H.; Oldfield, E.
Crystallographic structures of two bisphosphonate:1-deoxyxylulose-5-phosphate reductoisomerase complexes
J. Am. Chem. Soc.
126
10824-10825
2004
Escherichia coli (P45568)
Mac Sweeney, A.; Lange, R.; Fernandes, R.P.; Schulz, H.; Dale, G.E.; Douangamath, A.; Proteau, P.J.; Oefner, C.
The crystal structure of E. coli 1-deoxy-D-xylulose-5-phosphate reductoisomerase in a ternary complex with the antimalarial compound fosmidomycin and NADPH reveals a tight-binding closed enzyme conformation
J. Mol. Biol.
345
115-127
2005
Escherichia coli (P45568), Escherichia coli
Wong, A.; Munos, J.W.; Devasthali, V.; Johnson, K.A.; Liu, H.W.
Study of 1-deoxy-D-xylulose-5-phosphate reductoisomerase: synthesis and evaluation of fluorinated substrate analogues
Org. Lett.
6
3625-3628
2004
Escherichia coli
Fox, D.T.; Poulter, C.D.
Mechanistic studies with 2-C-methyl-D-erythritol 4-phosphate synthase from Escherichia coli
Biochemistry
44
8360-8368
2005
Escherichia coli
Merckle, L.; de Andres-Gomez, A.; Dick, B.; Cox, R.J.; Godfrey, C.R.
A fragment-based approach to understanding inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase
Chembiochem
6
1866-1874
2005
Escherichia coli (P45568)
Fox, D.T.; Poulter, C.D.
Synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphoric acid analogues as alternate substrates for methylerythritol phosphate synthase
J. Org. Chem.
70
1978-1985
2005
Escherichia coli
Walker, J.R.; Poulter, C.D.
Synthesis and evaluation of 1-deoxy-D-xylulose 5-phosphate analogues as chelation-based inhibitors of methylerythritol phosphate synthase
J. Org. Chem.
70
9955-9959
2005
Escherichia coli
Yajima, S.; Hara, K.; Iino, D.; Sasaki, Y.; Kuzuyama, T.; Ohsawa, K.; Seto, H.
Structure of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in a quaternary complex with a magnesium ion, NADPH and the antimalarial drug fosmidomycin
Acta Crystallogr. Sect. F
F63
466-470
2007
Escherichia coli (P45568), Escherichia coli
Wong, U.; Cox, R.J.
The chemical mechanism of D-1-deoxyxylulose-5-phosphate reductoisomerase from Escherichia coli
Angew. Chem. Int. Ed. Engl.
46
4926-4929
2007
Escherichia coli
Ortmann, R.; Wiesner, J.; Silber, K.; Klebe, G.; Jomaa, H.; Schlitzer, M.
Novel deoxyxylulosephosphate-reductoisomerase inhibitors: fosmidomycin derivatives with spacious acyl residues
Arch. Pharm.
340
483-490
2007
Escherichia coli (P45568)
Kaiser, J.; Yassin, M.; Prakash, S.; Safi, N.; Agami, M.; Lauw, S.; Ostrozhenkova, E.; Bacher, A.; Rohdich, F.; Eisenreich, W.; Safi, J.; Golan-Goldhirsh, A.
Anti-malarial drug targets: screening for inhibitors of 2C-methyl-D-erythritol 4-phosphate synthase (IspC protein) in Mediterranean plants
Phytomedicine
14
242-249
2007
Escherichia coli
Sando, T.; Takeno, S.; Watanabe, N.; Okumoto, H.; Kuzuyama, T.; Yamashita, A.; Hattori, M.; Ogasawara, N.; Fukusaki, E.; Kobayashi, A.
Cloning and characterization of the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway genes of a natural-rubber producing plant, Hevea brasiliensis
Biosci. Biotechnol. Biochem.
72
2903-2917
2008
Arabidopsis thaliana (Q9XFS9), Arabidopsis thaliana, Escherichia coli (P45568), Escherichia coli, Hevea brasiliensis (A9ZN08), Hevea brasiliensis
Giessmann, D.; Heidler, P.; Haemers, T.; Van Calenbergh, S.; Reichenberg, A.; Jomaa, H.; Weidemeyer, C.; Sanderbrand, S.; Wiesner, J.; Link, A.
Towards new antimalarial drugs: synthesis of non-hydrolyzable phosphate mimics as feed for a predictive QSAR study on 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors
Chem. Biodivers.
5
643-656
2008
Escherichia coli, Plasmodium falciparum
Perruchon, J.; Ortmann, R.; Altenkaemper, M.; Silber, K.; Wiesner, J.; Jomaa, H.; Klebe, G.; Schlitzer, M.
Studies addressing the importance of charge in the binding of fosmidomycin-like molecules to deoxyxylulosephosphate reductoisomerase
ChemMedChem
3
1232-1241
2008
Escherichia coli (P45568)
Lauw, S.; Illarionova, V.; Bacher, A.; Rohdich, F.; Eisenreich, W.
Biosynthesis of isoprenoids: studies on the mechanism of 2C-methyl-D-erythritol-4-phosphate synthase
FEBS J.
275
4060-4073
2008
Arabidopsis thaliana, Bacillus subtilis, Mycobacterium tuberculosis, Escherichia coli (P45568), Escherichia coli
Deng, L.; Sundriyal, S.; Rubio, V.; Shi, Z.Z.; Song, Y.
Coordination chemistry based approach to lipophilic inhibitors of 1-deoxy-D-xylulose-5-phosphate reductoisomerase
J. Med. Chem.
52
6539-6542
2009
Bacillus anthracis, Escherichia coli, Micrococcus luteus, Pseudomonas aeruginosa
Xue, J.; Diao, J.; Cai, G.; Deng, L.; Zheng, B.; Yao, Y.; Song, Y.
Antimalarial and structural studies of pyridine-containing inhibitors of 1-deoxyxylulose-5-phosphate reductoisomerase
ACS Med. Chem. Lett.
4
278-282
2013
Escherichia coli, Plasmodium falciparum (O96693), Plasmodium falciparum
Bodill, T.; Conibear, A.C.; Mutorwa, M.K.; Goble, J.L.; Blatch, G.L.; Lobb, K.A.; Klein, R.; Kaye, P.T.
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
Bioorg. Med. Chem.
21
4332-4341
2013
Escherichia coli, Plasmodium falciparum
Zingle, C.; Tritsch, D.; Grosdemange-Billiard, C.; Rohmer, M.
Catechol-rhodanine derivatives: Specific and promiscuous inhibitors of Escherichia coli deoxyxylulose phosphate reductoisomerase (DXR)
Bioorg. Med. Chem.
22
3713-3719
2014
Escherichia coli (Q1RG16), Escherichia coli, Escherichia coli UPEC (Q1RG16)
Li, H.; Tian, J.; Sun, W.; Qin, W.; Gao, W.Y.
Mechanistic insights into 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a key enzyme of the MEP terpenoid biosynthetic pathway
FEBS J.
280
5896-5905
2013
Escherichia coli (Q8X8Y1), Escherichia coli, Escherichia coli O157 (Q8X8Y1)
Hui, X.; Liu, H.; Tian, F.L.; Li, F.F.; Li, H.; Gao, W.Y.
Inhibition of green tea and the catechins against 1-deoxy-d-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway
Fitoterapia
113
80-84
2016
Escherichia coli
Hui, X.; Yue, Q.; Zhang, D.D.; Li, H.; Yang, S.Q.; Gao, W.Y.
Antimicrobial mechanism of theaflavins: They target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway
Sci. Rep.
6
38945
2016
Escherichia coli
Hui, X.; Hua, S.H.; Wu, Q.Q.; Li, H.; Gao, W.Y.
Antimicrobial mechanism of epigallocatechin gallate and gallocatechin gallate they target 1-deoxy-D-xylulose 5-phosphate reductoisomerase, the key enzyme of the MEP terpenoid biosynthetic pathway
Arch. Biochem. Biophys.
622
1-8
2017
Escherichia coli (P45568)
Munier, M.; Tritsch, D.; Krebs, F.; Esque, J.; Hemmerlin, A.; Rohmer, M.; Stote, R.; Grosdemange-Billiard, C.
Synthesis and biological evaluation of phosphate isosters of fosmidomycin and analogs as inhibitors of Escherichia coli and Mycobacterium smegmatis 1-deoxyxylulose 5-phosphate reductoisomerases
Bioorg. Med. Chem.
25
684-689
2017
Mycolicibacterium smegmatis (A0QVH7), Escherichia coli (P45568), Mycolicibacterium smegmatis ATCC 700084 (A0QVH7)
Kesharwani, S.; Sundriyal, S.
Non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) a critical review and future perspective
Eur. J. Med. Chem.
213
113055
2021
Escherichia coli (P45568), Mycobacterium tuberculosis (P9WNS1), Plasmodium falciparum (Q8IKG4), Mycobacterium tuberculosis H37Rv (P9WNS1), Mycobacterium tuberculosis ATCC 25618 (P9WNS1)
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Release 2023.1 (January 2023)
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