BRENDA home
History
Information on EC 1.1.1.267 - 1-deoxy-D-xylulose-5-phosphate reductoisomerase
for references in articles please use BRENDA:EC1.1.1.267Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
EC Tree
1.1.1.267 1-deoxy-D-xylulose-5-phosphate reductoisomeraseSpecify your search results
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 enzyme appears in viruses and cellular organisms
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
topPlease wait a moment until the data is sorted. This message will disappear when the data is sorted.
SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
1-deoxy-D-xylulose 5-phosphate isomeroreductase
-
-
-
-
1-deoxy-D-xylulose 5-phosphate reductoisomerase
1-deoxy-D-xylulose-5-phosphate reductoisomerase
1-deoxyxylulose 5-phosphate reductoisomerase
1-deoxyxylulose-5-phosphate reductoisomerase
2-C-methyl-D-erythritol 4-phosphate synthase
2C-methyl-D-erythritol-4-phosphate synthase
deoxyxylulose 5-phosphate reductoisomerase
DOXP reductoisomerase
DOXP-reductoisomerase
DXP reductoisomerase
DXR
DXR1
FtIspC
IspC
MEP synthase
MtbIspC
MtDXR
Rv2870c
VvDxr
YpIspC
2-C-methyl-D-erythritol 4-phosphate synthase
-
-
-
-
deoxyxylulose 5-phosphate reductoisomerase
-
-
-
-
DXP reductoisomerase
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 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+
Mycobacterium tuberculosis
-
-
-
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+
Synechocystis sp.
-
-
-
2-C-methyl-D-erythritol 4-phosphate + NADP+ = 1-deoxy-D-xylulose 5-phosphate + NADPH + H+
Mycobacterium tuberculosis H37Rv
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
PATHWAY SOURCE
PATHWAYS
BRENDA
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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].
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
CAS REGISTRY NUMBER
COMMENTARY
210756-42-6
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
1,2-dideoxy-D-threo-3-hexulose 6-phosphate + NADPH + H+
2-C-ethyl-D-erythritol 4-phosphate + NADP+
-
i.e. 1-methyl-1-deoxy-D-xylulose 5-phosphate or M-DXP, a substrate analogue whichis inactive with the wild-type but active with mutant W204F
-
-
?
1-deoxy-D-xylulose 5-phosphate + NAD(P)H + H+
2-C-methyl-D-erythritol 4-phosphate + NAD(P)+
1-deoxy-D-xylulose-5-phosphate + NADH
methyl-D-erythritol-4-phosphate + NAD+
-
-
-
-
r
1-deoxy-L-erythrulose + NADPH + H+
? + NADP+
-
reaction of the truncated substrate 1-deoxy-L-erythrulose in the presence and absence of phosphite dianion, overview
-
-
?
methyl-D-erythritol-4-phosphate + NADP+
1-deoxy-D-xylulose-5-phosphate + NADPH
-
-
-
-
r
1-deoxy-D-xylulose 5-phosphate + NAD(P)H + H+
2-C-methyl-D-erythritol 4-phosphate + NAD(P)+
the forward reaction is preferred
-
-
r
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 + NAD(P)H + H+
2-C-methyl-D-erythritol 4-phosphate + NAD(P)+
-
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NAD(P)H + H+
2-C-methyl-D-erythritol 4-phosphate + NAD(P)+
NADPH is the preferred cofactor
-
-
?
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+
second committed step in isopentenyl diphosphate biosynthesis via the plastidial nonmevalonate pathway of isoprenoid biosynthesis, overview
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
r
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+
-
-
-
?
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+
-
-
-
?
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+
-
involved in the biosynthesis of isopentenylphosphate
-
-
?
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+
-
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 + 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+
the enzyme catalyzes the second committed step in the 2C-methyl-D-erythritol 4-phosphate pathway for biosynthesis 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+
-
-
-
-
?
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+
-
first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway, overview
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
the forward direction is preferred
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
NADPH and 2-C-methyl-D-erythritol 4-phosphate bind to the free enzyme and the two bind together to generate a nonproductive ternary complex
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
Mycobacterium tuberculosis ATCC 25618
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway, overview
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
the forward direction is preferred
-
-
r
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+
-
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
?
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+
Mycolicibacterium smegmatis ATCC 700084
-
-
-
?
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+
-
-
-
?
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+
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate, overview
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
the enzyme catalyzes the first committed step in the biosynthesis of isopentenyl diphosphate in the plastidial 2C-methyl-D-erythritol 4-phosphate pathway leading to production of forskolin, overview
-
-
?
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+
MH018577
-
-
-
?
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+
-
second step of the methylerythritol 4-phosphate pathway
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
step in the methylerythritol 4-phosphate pathway
-
-
?
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+
-
-
-
-
?
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+
i.e. DXP
-
-
?
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+
i.e. DXP
-
-
?
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
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
?
1-deoxy-D-xylulose-5-phosphate + NADPH
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
r
1-deoxy-D-xylulose-5-phosphate + NADPH
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
r
1-deoxy-D-xylulose-5-phosphate + NADPH
methyl-D-erythritol-4-phosphate + NADP+
-
-
-
-
?
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
2C-methyl-D-erythritol 4-phosphate + 2C-methyl-D-erythritol 4-phosphate + NADP+
? + NADPH
-
in reaction mixtures containing 0.15â0.25 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 + 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 + 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
-
-
?
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
-
-
?
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
-
-
?
glycolaldehyde phosphate + hydroxyacetone + NADPH
? + NADP+
reaction mixtures containing 0.21-0.34 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
-
-
?
additional information
?
-
participation in the control of the 2-C-methyl-D-erythritol 4-phosphate pathway
-
-
?
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 206â216) is able to fold into at least three different conformations
-
-
?
additional information
?
-
-
used for the synthesis of [1-13C1]2C-methyl-D-erythritol 4-phosphate and [3-13C1]2C-methyl-D-erythritol 4-phosphate
-
-
?
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
?
-
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
?
-
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
-
-
?
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
?
-
-
DXR has rate-limiting roles in isopentenyl diphosphate and dimethylallyl diphosphate synthesis
-
-
?
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
?
-
-
development and evaluation of a high-throughput screening assay for simultaneous selection of inhibitors of the enzyme, overview
-
-
?
additional information
?
-
-
DXR is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway
-
-
?
additional information
?
-
DXR is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway
-
-
?
additional information
?
-
product identification by mass spectrometry (HPLC-MS)
-
-
-
additional information
?
-
-
product identification by mass spectrometry (HPLC-MS)
-
-
-
additional information
?
-
DXR can accelerate the biosynthesis of lycopene. DXR is an effective regulatory site for the synthesis and accumulation of diterpenoid compounds such as tanshinone
-
-
?
additional information
?
-
-
substrate synthesis and product identification method, overview
-
-
?
additional information
?
-
-
a retroaldol/aldol mechanism for the DXR catalyzed rearrangement of 1-deoxy-D-xylulose 5-phosphate to 2-C-methyl-D-erythritol 4-phosphate. DXR first cleaves the C3-C4 bond of 1-deoxy-D-xylulose 5-phosphate in a retroaldol manner to generate a three-carbon and a two-carbon phosphate bimolecular intermediate. These two species are then reunited by an aldol reaction to form a new C-C bond, yielding the same aldehyde intermediate methylerythrose phosphate. Subsequent reduction of methylerythrose phosphate by NADPH affords 2-C-methyl-D-erythritol 4-phosphate
-
-
?
additional information
?
-
-
mono-((2S,3S)-3-fluoromethyl-2,4-dihydroxy-3-methyl-butyl) ester is not a substrate for DXR
-
-
?
additional information
?
-
VvDxr residues S186, H209, S222, N227 and K228 may participate in binding of the DXP substrate's phosphate moiety. These residues are conserved. H209 is a part of a flexible loop (209-HPXWXMG-115) that closes on the active site upon substrate binding. While H209 interacts with the phosphate group, W211 and M213 shield the remaining part of Dxp from solvent
-
-
-
additional information
?
-
-
VvDxr residues S186, H209, S222, N227 and K228 may participate in binding of the DXP substrate's phosphate moiety. These residues are conserved. H209 is a part of a flexible loop (209-HPXWXMG-115) that closes on the active site upon substrate binding. While H209 interacts with the phosphate group, W211 and M213 shield the remaining part of Dxp from solvent
-
-
-
additional information
?
-
VvDxr residues S186, H209, S222, N227 and K228 may participate in binding of the DXP substrate's phosphate moiety. These residues are conserved. H209 is a part of a flexible loop (209-HPXWXMG-115) that closes on the active site upon substrate binding. While H209 interacts with the phosphate group, W211 and M213 shield the remaining part of Dxp from solvent
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
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
additional information
?
-
participation in the control of the 2-C-methyl-D-erythritol 4-phosphate pathway
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
second committed step in isopentenyl diphosphate biosynthesis via the plastidial nonmevalonate pathway of isoprenoid biosynthesis, overview
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
r
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+
-
-
-
?
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+
-
-
-
?
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+
-
involved in the biosynthesis of isopentenylphosphate
-
-
?
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+
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
the enzyme catalyzes the second committed step in the 2C-methyl-D-erythritol 4-phosphate pathway for biosynthesis of isopentenyl diphosphate
-
-
?
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+
-
-
-
-
?
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+
-
first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway, overview
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
Mycobacterium tuberculosis ATCC 25618
-
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
first committed step in the mevalonate-independent isopentenyl diphosphate biosynthetic pathway, overview
-
-
r
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate
-
-
?
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+
Mycolicibacterium smegmatis ATCC 700084
-
-
-
?
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+
-
-
-
?
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+
second step of the deoxyxylulose 5-phosphate/methylerythritol 4-phosphate pathway with end product isopentenylphosphate, overview
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
the enzyme catalyzes the first committed step in the biosynthesis of isopentenyl diphosphate in the plastidial 2C-methyl-D-erythritol 4-phosphate pathway leading to production of forskolin, overview
-
-
?
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+
MH018577
-
-
-
?
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+
-
second step of the methylerythritol 4-phosphate pathway
-
-
?
1-deoxy-D-xylulose 5-phosphate + NADPH + H+
2-C-methyl-D-erythritol 4-phosphate + NADP+
-
step in the methylerythritol 4-phosphate pathway
-
-
?
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+
-
-
-
?
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
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
NADPH has a vital role in tight binding of the inhibitor fosmidomycin within the enzyme active site
NADPH
sequence contains a highly conserved NADPH-binding motif in the N-terminal region
NADPH
the NADPH-binding domains are critical to the catalytic activity of DXR. Two highly conserved NADPH-binding domains, GSTGSIGT and LAAGSNV, locate in the N-terminal region of AvDXR
additional information
cofactor docking study with DXR, presence of conserved NADPH-binding motif (GSTGSIGT and LAAGSNV) in N-terminal end of the CaDXR protein sequence
-
additional information
-
cofactor docking study with DXR, presence of conserved NADPH-binding motif (GSTGSIGT and LAAGSNV) in N-terminal end of the CaDXR protein sequence
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Ca2+
activates, a divalent cation is required for activity, can partially substitute for Mn2+
Co2+
Mg2+
Mn2+
Zn2+
activates, a divalent cation is required for activity, can partially substitute for Mn2+
additional information
Co2+
activates, a divalent cation is required for activity, can partially substitute for Mn2+
Mg2+
a divalent cation is absolutely required, optimal at 10 mM, the enzyme prefers Mn2+ or Mg2+
Mg2+
the enzyme requires the presence of a divalent metal ion for activity
Mg2+
activates, a divalent cation is required for activity, can partially substitute for Mn2+
Mg2+
-
a divalent metal ion is absolutely required for activity, involved in catalysis
Mn2+
a divalent cation is absolutely required, the enzyme prefers Mn2+ or Mg2+
Mn2+
activates, a divalent cation is required for activity, best cation, can partially be substituted by other divalent cations
Mn2+
-
a divalent metal ion is absolutely required for activity, involved in catalysis
additional information
-
Mn2+, Ca2+, Co2+, Zn2+, and Fe2+ ions are unable to support activity
additional information
Dxrs require a divalent metal for their activity. The enzymes may use Mg2+ or Mn2+ cations. The enzyme forms a dimeric assembly and contains a metal ion in the active site. The residues coordinating the metal are parts of two highly conserved protein fragments: 148-PVDSEHXA-155 and 227-NKGLEXIE-234. The first of these fragments is bridging the N- and C-terminal domains. Residues E152 and E231 are the major residues involved in metal binding, and in three crystal structure cases they are the only amino acids involved in interactions with the metal. In the fourth case the metal ion is coordinated by D150, E152 and E231 (PDB ID 5KRR, chain B)
additional information
-
Dxrs require a divalent metal for their activity. The enzymes may use Mg2+ or Mn2+ cations. The enzyme forms a dimeric assembly and contains a metal ion in the active site. The residues coordinating the metal are parts of two highly conserved protein fragments: 148-PVDSEHXA-155 and 227-NKGLEXIE-234. The first of these fragments is bridging the N- and C-terminal domains. Residues E152 and E231 are the major residues involved in metal binding, and in three crystal structure cases they are the only amino acids involved in interactions with the metal. In the fourth case the metal ion is coordinated by D150, E152 and E231 (PDB ID 5KRR, chain B)
additional information
-
divalent cations required for acitvity, activity decreases in the following order: Co2+, Mn2+, Mg2+, Ba2+, Ca2+, Cu2+
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(2R)-3-[4-(hydroxymethyl)-4-[[4-(hydroxymethyl)phenyl]methyl]piperidin-1-yl]propane-1,2-diol
-
-
(2R)-3-[4-[2-[(cyclohexa-2,4-dien-1-yl)oxy]ethyl]-4-(hydroxymethyl)piperidin-1-yl]propane-1,2-diol
-
-
(2R)-3-[[[1-butyl-2-(cyclobutylmethanesulfonyl)-1H-imidazol-5-yl]methyl](methyl)amino]propane-1,2-diol
-
-
(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
(3-(hydroxy[(pentafluorophenyl)carbonyl]amino)propyl)phosphonic acid
-
(3-(N-hydroxyacetamido)-1-phenyl)propylphosphonic acid
92% inhibition at 0.1 mM
(3R)-1-(2,2-dimethylpropyl)-3-hydroxy-3-([[(5-methyl-4H-1,2,4-triazol-3-yl)methyl]amino]methyl)piperidin-2-one
-
-
(3S)-1-(cyclopropylmethyl)-3-([[(4,5-dimethyl-1,3-thiazol-2-yl)methyl]amino]methyl)-3-hydroxypiperidin-2-one
-
-
(3S,4R)-3-((2S)-1-(6,7-dimethoxy-4-(pyrrolidin-1-yl)-1,7,8,8a-tetrahydroquinazolin-2-yl)-4-hydroxybutan-2-yl)-4-hydroxytetrahydrothiophene 1,1-dioxide
-
-
(4-chloro-2-[[1-(2,3-dihydroxypropyl)piperidin-4-yl]oxy]phenyl)(piperidin-1-yl)methanone
-
-
(5R)-5-[1-[(2R)-2,3-dihydroxypropyl]piperidin-4-yl]-5-(3-phenylpropyl)imidazolidine-2,4-dione
-
-
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-[(2S)-2,3-dihydroxypropyl]-N-[3-(furan-2-yl)phenyl]piperidine-4-carboxamide
-
-
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'-[(8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone
-
3,3-dimethyl-11-phenyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one
the inhibitor is believed to hamper the captivating step of the synthetic pathway, as a result of which inadequacy of IPP pool will definitely foster the endurance of parasite in the intraerythrocytic stage
-
3-(N-hydroxyacetamido)-1-(3,4-dichlorophenyl)propylphosphonic acid
-
3-(N-hydroxyformamido)-1-(2-bromophenyl)propylphosphonic acid
93% inhibition at 0.1 mM
3-(N-hydroxyformamido)-1-(3,4-dichlorophenyl)propylphosphonic acid
-
4-(1-(4-hydroxy-2-oxo-2H-chromen-3-yl)-2-methylpropyl)-5-methyl-2-(4-nitrophenyl)-1,2-dihydro-3H-pyrazol-3-one
-
-
4-butyl-6-[4-([[(2R)-2,3-dihydroxypropyl](methyl)amino]methyl)phenyl]pyridin-2(1H)-one
-
-
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyacetamido)propyl)phosphonate
-
diethyl (1-(3,4-dichlorophenyl)-3-(N-hydroxyformamido)propyl)phosphonate
-
diethyl (3-[[3-(hydroxymethyl)phenyl]amino]-3-oxopropyl)phosphonate
-
17.9% inhibition
diethyl [3-(3-hydroxyanilino)-3-oxopropyl]phosphonate
49.2% inhibition at 0.25 mM
-
diethyl [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonate
-
33.5% inhibition
diethyl [3-[(3-methoxyphenyl)amino]-3-oxopropyl]phosphonate
-
14.1% inhibition
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
ethyl 1-[(2R)-2,3-dihydroxypropyl]-4-(2-phenoxyethyl)piperidine-4-carboxylate
-
-
ethyl 1-[(2R)-2,3-dihydroxypropyl]-4-[[2-(trifluoromethyl)phenyl]methyl]piperidine-4-carboxylate
-
-
ethyl 2-(2-ethoxy-2-oxoethyl)-2,5-dihydro-1H-benzo[b][1,4]diazepine-3-carboxylate
the inhibitor is believed to hamper the captivating step of the synthetic pathway, as a result of which inadequacy of IPP pool will definitely foster the endurance of parasite in the intraerythrocytic stage
-
ethyl hydrogen [1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonate
-
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonate
-
ethyl hydrogen [3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonate
20% inhibition at 0.1 mM
fosmidomycin analogues
synthesis, stereochemistry, and analysis of inhibitory potency of several fosmidomycin analogues, overview
-
methyl N-([(3S)-1-[(2,3-difluorophenyl)methyl]-3-hydroxy-2-oxopiperidin-3-yl]methyl)glycinate
-
-
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
phosphate mono-((2S,3S)-3-fluoromethyl-2,4-dihydroxy-3-methyl-butyl) ester
-
is a weak competitive inhibitor of DXR, most likely due to the steric hindrance caused by the substitution of a fluoromethylgroup for a hydroxyl group. Is not an irreversible inactivator (suicide inhibitor) for DXR, fails to act as a mechanism-based inactivator if the retroaldol/aldol mechanism is operative
theaflavin-3'-gallate
-
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
[(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
-
[(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
[2-(1-hydroxy-6-oxo-1,6-dihydropyridin-2-yl)ethyl]phosphonic acid
-
-
[2-(3-methoxyanilino)-2-oxoethyl]phosphonic acid
17.8% inhibition at 0.25 mM
-
[2-([1-[(2R)-2,3-dihydroxypropyl]piperidin-4-yl]oxy)phenyl](piperidin-1-yl)methanone
-
-
[2-[acetyl(hydroxy)amino]ethyl]phosphonic acid
74% inhibition at 0.1 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
-
[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-(1,4-dihydropyridin-4-yl)propyl]phosphonic acid
-
-
[3-[acetyl(hydroxy)amino]-1-(2-bromophenyl)propyl]phosphonic acid
38% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-(2-cyanophenyl)propyl]phosphonic acid
30% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-(2-methylphenyl)propyl]phosphonic acid
55% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-[2-(2-hydroxyethyl)phenyl]propyl]phosphonic acid
35% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-[2-(hydroxymethyl)phenyl]propyl]phosphonic acid
36% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-[2-(methoxymethyl)phenyl]propyl]phosphonic acid
30% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-[2-(pyridin-3-yl)phenyl]propyl]phosphonic acid
20% inhibition at 0.1 mM
[3-[acetyl(hydroxy)amino]-1-[2-(thiophen-2-yl)phenyl]propyl]phosphonic acid
30% inhibition at 0.1 mM
[3-[acetyl(naphthalen-2-ylmethoxy)amino]propyl]phosphonic acid
compound binds to both the NADPH and DXP sites, while whole-cell inhibitory activity is relatively poor
[3-[hydroxy(3-phenylpropanoyl)amino]propyl]phosphonic acid
-
compound binds to Dxr via a non-bisubstrate mechanism. The diethyl ester of [3-[hydroxy(3-phenylpropanoyl)amino]propyl]phosphonic acid inhibits Mycobacterium tuberculosis growth
[4-[acetyl(hydroxy)amino]butyl]phosphonic acid
80% inhibition at 0.1 mM
-
[[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate
50% inhibition at 0.007 mM
(4-[[3-(hydroxymethyl)phenyl]amino]-4-oxobutyl)phosphonic acid
-
26.8% inhibition
1,2-dideoxy-D-threo-3-hexulose 6-phosphate
-
weak, competitive inhibition, a highly conserved tryptophan residue in the flexible loop is blocked by the substrate analog
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole
i.e. PPT, lead molecule as inhibitor of IspC
-
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole
i.e. PPT, lead molecule as inhibitor of IspC
-
1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole
i.e. PPT, lead molecule as inhibitor of IspC
-
1-hydroxy-5-phenylpyridin-2(1H)-one
-
minimal inhibitory concentration for growth 0.02 mM
1-hydroxy-5-phenylpyridin-2(1H)-one
-
minimal inhibitory concentration for growth 0.1 mM
1-hydroxy-5-phenylpyridin-2(1H)-one
-
minimal inhibitory concentration for growth 0.1 mM
1-hydroxy-5-phenylpyridin-2(1H)-one
-
minimal inhibitory concentration for growth 0.05 mM
13-methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-i]phenanthridinium chloride
i.e. sanguinarine chloride, lead molecule as inhibitor of IspC
-
13-methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-i]phenanthridinium chloride
i.e. sanguinarine chloride, lead molecule as inhibitor of IspC
-
13-methyl-[1,3]benzodioxolo[5,6-c]-1,3-dioxolo[4,5-i]phenanthridinium chloride
i.e. sanguinarine chloride, lead molecule as inhibitor of IspC
-
3'-[(8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone
i.e. rottlerin, lead molecule as inhibitor of IspC
-
3'-[(8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone
i.e. rottlerin, lead molecule as inhibitor of IspC
-
3'-[(8-cinnamoyl-5,7-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-yl)methyl]-2',4',6'-trihydroxy-5'-methylacetophenone
i.e. rottlerin, lead molecule as inhibitor of IspC
-
3-(3,5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)
i.e. GW5074, lead molecule as inhibitor of IspC
-
3-(3,5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)
i.e. GW5074, lead molecule as inhibitor of IspC
-
3-(3,5-dibromo-4-hydroxybenzylidine-5-iodo-1,3-dihydro-indol-2-one)
i.e. GW5074, lead molecule as inhibitor of IspC
-
3-(hydroxy([(2-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid
-
-
3-(hydroxy([(3-methylbutanoyl)amino]acetyl)amino)propylphosphonic acid
-
-
3-(hydroxy([(4-phenoxybutanoyl)amino]acetyl)amino)propylphosphonic acid
-
-
3-(hydroxy([(4-phenylbutanoyl)amino]acetyl)amino)propylphosphonic acid
-
-
3-[(([(3,4-dimethoxyphenyl)acetyl]amino)acetyl)(hydroxy)amino]propylphosphonic acid
-
-
3-[(([(3,4-dimethoxyphenyl)acetyl]amino)acetyl)(hydroxy)amino]propylphosphonic acid
-
-
3-[([(cyclopropylcarbonyl)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(([3-(trifluoromethoxy)benzoyl]amino)acetyl)amino]propylphosphonic acid
-
-
3-[hydroxy(([4-(1H-indol-3-yl)butanoyl]amino)acetyl)amino]propylphosphonic acid
-
-
3-[hydroxy(([4-(1H-indol-3-yl)butanoyl]amino)acetyl)amino]propylphosphonic acid
-
-
4-benzylbenzene-1,2-diol
-
minimal inhibitory concentration for growth 0.2 mM
4-benzylbenzene-1,2-diol
-
minimal inhibitory concentration for growth 0.2 mM
4-benzylbenzene-1,2-diol
-
minimal inhibitory concentration for growth 0.2 mM
biphenyl-3,4-diol
-
minimal inhibitory concentration for growth 0.2 mM
diethyl (2-[[3-(hydroxymethyl)phenyl]amino]-2-oxoethyl)phosphonate
-
40.4% inhibition
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate
43.9% inhibition at 0.25 mM
diethyl [2-(3-hydroxyanilino)-2-oxoethyl]phosphonate
45.2% inhibition at 0.25 mM
diethyl [2-[(3-hydroxyphenyl)amino]-2-oxoethyl]phosphonate
-
24.4% inhibition
diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate
40.4% inhibition at 0.25 mM
-
diethyl [2-[3-(hydroxymethyl)anilino]-2-oxoethyl]phosphonate
40.7% inhibition at 0.25 mM
-
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 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
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
-
IC50: 310 nM for the forward reaction, 0.0027 mM for the reverse reaction, Gram positive bacteria, including Mycobacterium tuberculosis, are resistant against the antibiotic fosmidomycin, which is an inhibitor of the enzyme from most gram-negative bacteria and other organisms
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
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
fosmidomycin
a natural antibiotic from Streptomyces lavendulae, a specific, mixed type inhibitor, the N-formyl-N-hydroxy amino headgroup of fosmidomycin coordinates Mg2+ ion forming an octahedral complex with active site residues Asp157, Glu159, and Glu241 and a critical binding site water molecule, residue His219 is essential for placing fosmidomycin in the active site for optimal catalysis, mechanism, overview, NADPH has a vital role in tight binding of the inhibitor within the enzyme active site
fosmidomycin
analysis of parasite growth in infected cultured erythrocytes. 50% growth inhibition at about 301 nM
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
fosmidomycin
the DXR inhibitor shows safety as well as efficacy against Plasmodium falciparum malaria in clinical trials
fosmidomycin
IC50: 450 nM, recombinant enzyme, inhibition of growth and forskolin production in vivo
fosmidomycin
-
potent inhibitor but with very short half-life in plasma and low oral availability
FR-900098
a naturally occurring retrohydroxamate phosphonic acid, isolated from the filtrate of a Pseudomonas fluorescens PK-52 culture
FR900098
analysis of parasite growth in infected cultured erythrocytes. 50% growth inhibition at about 118 nM
gallocatechin gallate
-
completely suppresses the activity of DXR at 100 microM, and shows around 50% DXR inhibition at 25 microM
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
theaflavin-3,3'-digallate
-
non-competitive against 1-deoxy-D-xylulose 5-phosphate and un-competitive inhibitors with respect to NADPH
theaflavin-3,3'-digallate
strong inhibition of DXR, isolated from Camellia sinenesis
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid
-
-
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid
-
-
[(3,4-dichlorophenyl)([2-[hydroxy(methyl)amino]-2-oxoethyl]sulfanyl)methyl]phosphonic acid
-
-
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
-
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
conformation of inhibitor within the MtDXR active site (PDB ID 2Y1D)
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
inhibition of strain D2d
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid
-
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid
inhibition of strain D2d
[3-[acetyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
-
[3-[acetyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
-
[3-[formyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
-
[3-[formyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
-
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
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
-
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
-
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
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
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
the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues. MEP pathway inhibitors (collectively called MEPicides) are most often rationally designed on the fosmidomycin scaffold, balancing target specificity with bioavailability. Pilot scale high-throughput screening (HTS) campaign against the first and second committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD), using compounds present in the commercially available LOPAC1280 library as well as in an in-house natural product extract library. Analysis of mechanism of inhibition, most compounds function through aggregation. The method is useful for quickly screening a chemical library, while effectively identifying false positive compounds associated with assay constraints and aggregation. Screening using Yersinia pestis subsp. A1122, Mycobacterium tuberculosis, and Francisella tularensis subsp. novicida strain Utah 112, overview. Inhibition is attenuated in the presence of Triton X-100 for all inhibitors except sanguinarine chloride and suramin hexasodium
-
additional information
-
no substrate inhibition by 2-C-methyl-D-erythritol 4-phosphate, NADPH or NADP+
-
additional information
-
development and evaluation of a high-throughput screening spectrometric assay, measuring Dxr activity of Dxr coupled with 1-deoxy-D-xylulose-5-phosphate synthase, Dxs, activity, for simultaneous selection of inhibitors of the enzyme, overview
-
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
-
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
-
additional information
-
use of the Dxr-fosmidomycin cocrystal structure to design bisubstrate ligands to bind to both the 1-deoxy-D-xylulose-5-phosphate and NADPH sites
-
additional information
the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues. MEP pathway inhibitors (collectively called MEPicides) are most often rationally designed on the fosmidomycin scaffold, balancing target specificity with bioavailability. Pilot scale high-throughput screening (HTS) campaign against the first and second committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD), using compounds present in the commercially available LOPAC1280 library as well as in an in-house natural product extract library. Analysis of mechanism of inhibition, most compounds function through aggregation. The method is useful for quickly screening a chemical library, while effectively identifying false positive compounds associated with assay constraints and aggregation. Screening using Yersinia pestis subsp. A1122, Mycobacterium tuberculosis, and Francisella tularensis subsp. novicida strain Utah 112, overview. Inhibition is attenuated in the presence of Triton X-100 for all inhibitors except sanguinarine chloride and suramin hexasodium
-
additional information
non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview
-
additional information
hydroxamate analogues of fosfoxacin, the phosphate homologue of fosmidomycin, as inhibitors of DXR, synthesis and activities, overview
-
additional information
design and development of inhibitors, structure and docking modeling, overview
-
additional information
-
design and development of inhibitors, structure and docking modeling, overview
-
additional information
pyridine-containing fosmidomycin derivative inhibitor design and development using quantitative structure?activity relationship and crystallographic studies, synthesis, overview
-
additional information
-
pyridine-containing fosmidomycin derivative inhibitor design and development using quantitative structure?activity relationship and crystallographic studies, synthesis, overview
-
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 [3-[(3-hydroxyphenyl)amino]-3-oxopropyl]phosphonate, diethyl [2-[(3-methoxyphenyl)amino]-2-oxoethyl]phosphonate, diethyl [3-[(3-methoxyphenyl)amino]-3-oxopropyl]phosphonate, diethyl [2-[(3-bromophenyl)amino]-2-oxoethyl]phosphonate, diethyl (3-[[3-(hydroxymethyl)phenyl]amino]-3-oxopropyl)phosphonate, [4-[(3-methoxyphenyl)amino]-4-oxobutyl]phosphonic acid, and [2-[(3-cyanophenyl)amino]-2-oxoethyl]phosphonic acid
-
additional information
non-hydroxamate inhibitors of 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), docking study, structure-activity analysis, overview
-
additional information
in silico identification and biological evaluation of inhibitors targeting 1-deoxy-D-xylulose-5-phosphate reductoisomerase, structure-based computational approach and biological evaluation, docking and binding mode estimation and molecular dynamics simulation, overview. Inhibitor screening in different database sources such as ZINC, NCI, ChemDB, PubChem, and Drugbank
-
additional information
computational design of potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and prediction of pharmacokinetics and pharmacodynamics, active site binding, molecular docking, and complex-based pharmacophore modeling, binding structures, overview
-
additional information
-
computational design of potent inhibitors for deoxyxylulose 5-phosphate reductoisomerase and prediction of pharmacokinetics and pharmacodynamics, active site binding, molecular docking, and complex-based pharmacophore modeling, binding structures, overview
-
additional information
-
inhibitor design and synthesis, structure-activity relationship profile for the inhibition of TgDXR, overview
-
additional information
the methyl erythritol phosphate (MEP) pathway represents an attractive series of targets for antibiotic design, considering each enzyme of the pathway is both essential and has no human homologues. MEP pathway inhibitors (collectively called MEPicides) are most often rationally designed on the fosmidomycin scaffold, balancing target specificity with bioavailability. Pilot scale high-throughput screening (HTS) campaign against the first and second committed steps in the pathway, catalyzed by DXP reductoisomerase (IspC) and MEP cytidylyltransferase (IspD), using compounds present in the commercially available LOPAC1280 library as well as in an in-house natural product extract library. Analysis of mechanism of inhibition, most compounds function through aggregation. The method is useful for quickly screening a chemical library, while effectively identifying false positive compounds associated with assay constraints and aggregation. Screening using Yersinia pestis strain A1122, Mycobacterium tuberculosis, and Francisella tularensis subsp. novicida strain Utah 112, overview. Inhibition is attenuated in the presence of Triton X-100 for all inhibitors except sanguinarine chloride and suramin hexasodium
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
salicylic acid
strongly induces DXR in leaves, reaches the highest level after 48 h of the treatment, and gradually decreases after. Is induced by salicylic acid at least at transcriptional level
methyl jasmonate
strong induction, reaching the highest level after 24 h of the treatment, and gradually decreasing thereafter
additional information
-
transcript accumulation of DXR gene is regulated by mechanical wounding and fungal elicitors. Expression of the DXR gene in rubber trees is not induced by light
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Infections
Resistance of the Burkholderia cepacia complex to fosmidomycin and fosmidomycin derivatives.
Malaria
In silico identification of promiscuous scaffolds as potential inhibitors of 1-deoxy-d-xylulose 5-phosphate reductoisomerase for treatment of Falciparum malaria.
Malaria
Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum.
Malaria
Molecular epidemiology of malaria in Cameroon. XXV. In vitro activity of fosmidomycin and its derivatives against fresh clinical isolates of Plasmodium falciparum and sequence analysis of 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
Malaria
Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum.
Malaria
The druggable antimalarial target PfDXR: overproduction strategies and kinetic characterization.
Tuberculosis
1-Deoxy-D-xylulose 5-phosphate reductoisomerase (IspC) from Mycobacterium tuberculosis: towards understanding mycobacterial resistance to fosmidomycin.
Tuberculosis
A High-Throughput Screening Assay for Simultaneous Selection of Inhibitors of Mycobacterium tuberculosis 1-Deoxy-D-Xylulose-5-Phosphate Synthase (Dxs) or 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr).
Tuberculosis
Alteration of the flexible loop in 1-deoxy-D-xylulose-5-phosphate reductoisomerase boosts enthalpy-driven inhibition by fosmidomycin.
Tuberculosis
Biosynthesis of isoprenoids: studies on the mechanism of 2C-methyl-D-erythritol-4-phosphate synthase.
Tuberculosis
Conformational dynamics of the flexible catalytic loop in Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase.
Tuberculosis
Design of Potential Bisubstrate Inhibitors against Mycobacterium tuberculosis (Mtb) 1-Deoxy-D-Xylulose 5-Phosphate Reductoisomerase (Dxr)-Evidence of a Novel Binding Mode.
Tuberculosis
Design, Synthesis, and X-ray Crystallographic Studies of ?-Aryl Substituted Fosmidomycin Analogues as Inhibitors of Mycobacterium tuberculosis 1-Deoxy-d-xylulose 5-Phosphate Reductoisomerase.
Tuberculosis
Dxr is essential in Mycobacterium tuberculosis and fosmidomycin resistance is due to a lack of uptake.
Tuberculosis
Highly precise measurement of kinetic isotope effects using 1H-detected 2D [13C,1H]-HSQC NMR spectroscopy.
Tuberculosis
Inhibition of 1-deoxy-D-xylulose-5-phosphate reductoisomerase by lipophilic phosphonates: SAR, QSAR, and crystallographic studies.
Tuberculosis
Kinetic and chemical mechanism of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate isomeroreductase.
Tuberculosis
Pre-Steady-State Kinetic Analysis of 1-Deoxy-d-xylulose-5-phosphate Reductoisomerase from Mycobacterium tuberculosis Reveals Partially Rate-Limiting Product Release by Parallel Pathways.
Tuberculosis
Structures of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase provide new insights into catalysis.
Tuberculosis
Substitution of the phosphonic acid and hydroxamic acid functionalities of the DXR inhibitor FR900098: An attempt to improve the activity against Mycobacterium tuberculosis.
Tuberculosis
Synthesis of functionalized cinnamaldehyde derivatives by an oxidative Heck reaction and their use as starting materials for preparation of Mycobacterium tuberculosis 1-deoxy-D-xylulose-5-phosphate reductoisomerase inhibitors.
Tuberculosis
The 1.9 A resolution structure of Mycobacterium tuberculosis 1-deoxy-D-xylulose 5-phosphate reductoisomerase, a potential drug target.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.3
1,2-dideoxy-D-threo-3-hexulose 6-phosphate
-
pH 7.8, 37°C, recombinant mutant W204F
53
1-deoxy-L-erythrulose
-
pH 7.5, 25°C, recombinant enzyme in absence or presence of phosphite dianion
0.227
1-fluoro-1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
0.147
1-deoxy-D-xylulose 5-phosphate
pH 8.0, 37°C, recombinant enzyme
0.17
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant wild-type enzyme
0.137
1-deoxy-D-xylulose 5-phosphate
wild-type, pH 7.5, 25°C
0.39
1-deoxy-D-xylulose 5-phosphate
mutant W203Y, pH 7.5, 25°C
12
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204A
0.132
1-deoxy-D-xylulose 5-phosphate
pH 8.0, 37°C, recombinant pseudomature enzyme
0.081
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant His-tagged enzyme
0.115
1-deoxy-D-xylulose 5-phosphate
-
pH 7.5, 25°C, recombinant enzyme
2.9
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204L
0.42
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204F
1.015
1-deoxy-D-xylulose 5-phosphate
mutant W203F, pH 7.5, 25°C
0.0471
1-deoxy-D-xylulose 5-phosphate
-
pH 7.9, 30°C, recombinant His-tagged enzyme
0.05
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADH, presence of Co2+, pH 7.5, 25°C
0.063
1-deoxy-D-xylulose-5-phosphate
-
pH 7.5, 37°C, presence of 1 mM Co2+
0.1
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADPH, presence of Mn2+, pH 7.5, 25°C
0.004
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADPH, presence of Co2+, pH 7.5, 25°C
0.21
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADH, presence of Mg2+, pH 7.5, 25°C
0.042
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADPH, presence of Mg2+, pH 7.5, 25°C
0.24
1-deoxy-D-xylulose-5-phosphate
-
cosubstrate NADH, presence of Mn2+, pH 7.5, 25°C
0.134
1-deoxy-D-xylulose-5-phosphate
-
pH 7.5, 37°C, presence of 1 mM Mg2+
0.195
1-deoxy-D-xylulose-5-phosphate
-
pH 7.5, 37°C, presence of 1 mM Mn2+
0.174
2-C-methyl-D-erythritol 4-phosphate
-
pH 7.9, 30°C, recombinant His-tagged enzyme
0.084
2-C-methyl-D-erythritol 4-phosphate
-
pH 7.5, 25°C, recombinant enzyme
0.972
2-C-methyl-D-erythritol 4-phosphate
pH 8.0, 37°C, recombinant pseudomature enzyme
0.042
methyl-D-erythritol-4-phosphate
-
presence of Mg2+, pH 7.5, 25°C
0.42
NADP+
-
pH 7.5, 25°C, recombinant enzyme, with substrate 1-deoxy-D-xylulose 5-phosphate
0.0098
NADPH
-
pH 7.5, 25°C, recombinant enzyme, with substrate 1-deoxy-D-xylulose 5-phosphate
additional information
additional information
-
kinetics, recombinant His-tagged wild-type and mutant enzymes
-
additional information
additional information
-
steady-state and single-turnover kinetics, primary kinetic isotope effects, overview
-
additional information
additional information
-
transient kinetics and kinetic mechanism, stopped-flow fluorescence measurements, overview. Kinetics of pre-steady-state reactions and steady-state kinetics, comparison of simulated and experimental values, burst kinetics model for pre-steady-state kinetics
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.04
1,2-dideoxy-D-threo-3-hexulose 6-phosphate
-
pH 7.8, 37°C, recombinant mutant W204F
37
1-fluoro-1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
0.26
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204L
10
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204F
17
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant wild-type enzyme
0.16
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204A
33
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant His-tagged enzyme
1.59
1-deoxy-D-xylulose 5-phosphate
mutant W203F, pH 7.5, 25°C
4.2
1-deoxy-D-xylulose 5-phosphate
wild-type, pH 7.5, 25°C
4.4
1-deoxy-D-xylulose 5-phosphate
pH 8.0, 37°C, recombinant pseudomature enzyme
29
1-deoxy-D-xylulose 5-phosphate
-
pH 7.6, 37°C, recombinant enzyme
3.54
1-deoxy-D-xylulose 5-phosphate
mutant W203Y, pH 7.5, 25°C
5.25
1-deoxy-D-xylulose 5-phosphate
-
pH 7.5, 25°C, recombinant enzyme
0.54
1-deoxy-D-xylulose 5-phosphate
-
pH 7.8, 37°C, recombinant mutant W204V
0.00155
1-deoxy-L-erythrulose
-
pH 7.5, 25°C, recombinant enzyme in absence of phosphite dianion
0.00086
1-deoxy-L-erythrulose
-
pH 7.5, 25°C, recombinant enzyme in presence of phosphite dianion
1.6
2-C-methyl-D-erythritol 4-phosphate
pH 8.0, 37°C, recombinant pseudomature enzyme
0.95
2-C-methyl-D-erythritol 4-phosphate
-
pH 7.5, 25°C, recombinant enzyme
0.95
NADP+
-
pH 7.5, 25°C, recombinant enzyme, with substrate 1-deoxy-D-xylulose 5-phosphate
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
11.3
2-C-methyl-D-erythritol 4-phosphate
-
pH 7.5, 25°C, recombinant enzyme
5.7
NADP+
-
pH 7.5, 25°C, recombinant enzyme, with substrate 1-deoxy-D-xylulose 5-phosphate
540
NADPH
-
pH 7.5, 25°C, recombinant enzyme, with substrate 1-deoxy-D-xylulose 5-phosphate
46
1-deoxy-D-xylulose 5-phosphate
-
pH 7.5, 25°C, recombinant enzyme
9.1
1-deoxy-D-xylulose 5-phosphate
mutant W203Y, pH 7.5, 25°C
1.46
1-deoxy-D-xylulose 5-phosphate
mutant W203F, pH 7.5, 25°C
0.0000292
1-deoxy-L-erythrulose
-
pH 7.5, 25°C, recombinant enzyme in absence of phosphite dianion
0.000163
1-deoxy-L-erythrulose
-
pH 7.5, 25°C, recombinant enzyme in presence of phosphite dianion
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
6.5
(3-acetamidopropyl)phosphonic acid
pH and temperature not specified in the publication
-
0.0041
(pyridin-2-ylmethyl)phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
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
0.63
1,2-dideoxy-D-threo-3-hexulose 6-phosphate
-
pH 7.8, 37°C, recombinant wild-type enzyme
1.1
1-deoxy-D-xylulose 5-phosphate
-
pH 7.9, 30°C, recombinant His-tagged enzyme
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
0.000002
phosphoric acid mono-[2-(N-acetyl-N-hydroxy-amino)-ethyl]-ester
-
pH 7.5, 37°C
0.0021
[(5-phenylpyridin-2-yl)methyl]phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
0.000077
[1-(3,4-dichlorophenyl)-3-[formyl(hydroxy)amino]propyl]phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
0.00022
[3-[acetyl(hydroxy)amino]-1-(3,4-dichlorophenyl)propyl]phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
0.0014
1-hydroxy-5-phenylpyridin-2(1H)-one
-
pH not specified in the publication, temperature not specified in the publication
0.0256
1-hydroxy-5-phenylpyridin-2(1H)-one
-
pH 7.6, 30°C, recombinant enzyme
0.1794
epigallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, uncompetitive versus NADPH
0.1483
epigallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, competitive versus 1-deoxy-D-xylulose 5-phosphate
0.000085
fosmidomycin
pH 8.0, 37°C, recombinant pseudomature enzyme
0.000034
fosmidomycin
-
pH 7.5, 22°C, IC50 versus proliferation of Plasmodium falciparum strain Dd2
0.0252
gallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, competitive versus 1-deoxy-D-xylulose 5-phosphate
0.0234
gallocatechin gallate
pH 7.0, 37°C, recombinant enzyme, uncompetitive versus NADPH
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
0.0000019
[3-[acetyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
pH 7.5, 22°C
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
0.00097
[3-[acetyl(hydroxy)amino]-1-(pyridin-3-yl)propyl]phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
0.000013
[3-[acetyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
pH 7.5, 22°C
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
0.00053
[3-[acetyl(hydroxy)amino]-1-(pyridin-4-yl)propyl]phosphonic acid
-
pH 7.6, 30°C, recombinant enzyme
0.000085
[3-[acetyl(hydroxy)amino]-1-phenylpropyl]phosphonic acid
pH 7.5, 22°C