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Information on EC 1.1.1.86 - ketol-acid reductoisomerase (NADP+) and Organism(s) Oryza sativa and UniProt Accession Q65XK0
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1.1.1.86 ketol-acid reductoisomerase (NADP+)IUBMB Comments
Also catalyses the reduction of 2-ethyl-2-hydroxy-3-oxobutanoate to 2,3-dihydroxy-3-methylpentanoate. The enzyme, found in many bacteria and archaea, is specific for NADPH (cf. EC 1.1.1.382, ketol-acid reductoisomerase (NAD+) and EC 1.1.1.383, ketol-acid reductoisomerase [NAD(P)+]).
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Word Map
- 1.1.1.86
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branched-chain
- 5-phosphate
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karis
- 1-deoxy-d-xylulose
- fosmidomycin
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isoprenoids
- methylerythritol
- 1-deoxy-d-xylulose-5-phosphate
- deoxyxylulose
- l-valine
- isobutanol
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2-c-methyl-d-erythritol
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non-mevalonate
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dihydroxyacid
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2-keto
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isoleucine-valine
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ilvbnce
- drug development
- biofuel production
- industry
The taxonomic range for the selected organisms is: Oryza sativa
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Synonyms
reductoisomerase, ketol-acid reductoisomerase, acetohydroxy acid isomeroreductase, ilv5p, isomeroreductase, acetohydroxyacid isomeroreductase, ahair, acetohydroxy acid reductoisomerase, ilvc1, acetolactate reductoisomerase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2-hydroxy-3-keto acid reductoisomerase
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acetohydroxy acid isomeroreductase
acetohydroxy acid reductoisomerase
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acetohydroxy-acid isomeroreductase
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acetohydroxy-acid reductoisomerase
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acetolactate reductoisomerase
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alpha-keto-beta-hydroxylacil reductoisomerase
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alpha-keto-beta-hydroxylacyl reductoisomerase
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dehydrogenase, dihydroxyisovalerate (isomerizing)
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dihydroxyisovalerate dehydrogenase (isomerizing)
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isomerase, ketol acid reducto-
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isomeroreductase
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KARI
reductoisomerase
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acetohydroxy acid isomeroreductase
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KARI
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
active site structure and catalytic mechanism, mechanism of induced fit, overview
(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+ = (2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
catalytic mechanism, overview
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
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oxidation
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reduction
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rearrangement
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PATHWAY SOURCE
PATHWAYS
KEGG
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-, -, -, -
SYSTEMATIC NAME
IUBMB Comments
(R)-2,3-dihydroxy-3-methylbutanoate:NADP+ oxidoreductase (isomerizing)
Also catalyses the reduction of 2-ethyl-2-hydroxy-3-oxobutanoate to 2,3-dihydroxy-3-methylpentanoate. The enzyme, found in many bacteria and archaea, is specific for NADPH (cf. EC 1.1.1.382, ketol-acid reductoisomerase (NAD+) and EC 1.1.1.383, ketol-acid reductoisomerase [NAD(P)+]).
CAS REGISTRY NUMBER
COMMENTARY
9075-02-9
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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
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
2-aceto-2-hydroxybutyrate + NADP+
(2R,3R)-2,3-dihydroxy-3-methylvalerate + NADPH + H+
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r
2-acetolactate + NADP+
(2R)-2,3-dihydroxy-3-isovalerate + NADPH + H+
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r
(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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-
-
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r
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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-
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r
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
conformational changes in a plant ketol-acid reductoisomerase upon Mg2+ and NADPH binding, overview
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r
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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r
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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the enzyme performs a two-step reaction of an alkyl migration followed by an NADPH-dependent reduction rection
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r
additional information
?
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KARI catalyzes two reactions: alkyl migration and reduction. Structure-function relationship, effects of ligand binding, MG2+ and NADPH, on the enzyme conformation, overview
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?
additional information
?
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KARI catalyzes two reactions: alkyl migration and reduction. Structure-function relationship, effects of ligand binding, MG2+ and NADPH, on the enzyme conformation, overview
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?
additional information
?
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structure-biological activity relationship, overview
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?
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
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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r
(2R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(2S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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r
(R)-2,3-dihydroxy-3-methylbutanoate + NADP+
(S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH + H+
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r
additional information
?
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structure-biological activity relationship, overview
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
NADPH
required, the majority of the NADP+ molecule binds to the N-domain of KARI with polar contacts with 11 residues, including W133, G134, S135, Q136, R162, S165, S167, S201, D202, Q205, and G254. There are also contacts with the C-domain, although these are much fewer and involve only the phosphoryl oxygen atoms and the oxygen and nitrogen atoms of the nicotinamide group in NADPH, forming contacts with C517, S518, and T519, and with R589 in the polypeptide
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Mg2+
Mg2+
additional information
Mg2+
required for the alkyl migration reaction, Km is 0.0072 mM, binding structure, overview
additional information
the enzyme catalyzes a two-step reaction: an alkyl migration that requires Mg2+, and a reduction reaction involving NADPH. For the reduction reaction, a divalent metal ion is also required, with any of Mg2+, Mn2+, Co2+, or Ni2+ utilized in this role
additional information
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the enzyme catalyzes a two-step reaction: an alkyl migration that requires Mg2+, and a reduction reaction involving NADPH. For the reduction reaction, a divalent metal ion is also required, with any of Mg2+, Mn2+, Co2+, or Ni2+ utilized in this role
additional information
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the NADPH reaction step requires a divalent cation, e.g. Mg2+, Mn2+, or Co2+, but in a non-specific manner
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cyclopropane-1,1-dicarboxylate
a competitive slow-, tight-binding inhibitor
2-(4-benzylpiperazin-1-yl)-N-(3,4-dichlorophenyl)acetamide
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48.1% inhibition at 200 microg/ml
2-dimethylphosphinoyl-2-hydroxyacetate
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i.e. Hoe 704, potent competitive inhibitor in vitro but weak in vivo
2-[[(4-methoxyphenyl)carbonyl]amino]benzoic acid
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57.4% inhibition at 200 microg/ml
4,4'-(pentamethylenedioxy)dibenzamidne bis(2-hydroxyethanesulfonate)
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binding structure and inhibition mechanism, overview
N'-(5-(3-pyridinyl)-1,3,4-thiadiazol-2-yl)-N-cyclopropyformyl-thiourea
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N'-(5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl)-N-cyclopropyformyl-thiourea
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N-Hydroxy-N-isopropyloxamate
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i.e. IpOHA, potent competitive inhibitor in vitro but weak in vivo
additional information
no inhibition by 1-aminocyclopropanecarboxylate, 1-methylcyclopropanecarboxylate, 2-methylcyclopropanecarboxylate, cyclopropane-1,2-dicarboxylate, and cyclopropanecarboxylate dimethyl ester
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additional information
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no inhibition by N'-(5-methyl-1,3,4-thiadiazol-2-yl)-N-cyclopropyformyl-thiourea, N'-(5-ethyl-1,3,4-thiadiazol-2-yl)-N-cyclopropyformyl-thiourea, and N'-(5-propyl-1,3,4-thiadiazol-2-yl)-N-cyclopropyformyl-thiourea
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additional information
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high throughput receptor-based virtual screening of the ZINC/drug like database based on the crystal structure of ketol-acid reductoisomerase/N-hydroxy-N-isopropyloxamate complex, PDB entry 1YVE
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KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
4.16
3-hydroxypyruvate
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at pH 8.0, temperature not specified in the publication
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0203
1-aminocarbonylcyclopropanecarboxylate
pH 8.0, 30°C, recombinant enzyme
0.0000903
cyclopropane-1,1-dicarboxylate
pH 8.0, 30°C, recombinant enzyme, versus hydroxypyruvate
additional information
additional information
inhibition mechanism and kinetics
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0.0025
ethylene glycol
pH 8.0, 30°C, recombinant enzyme, competitive mode
0.0032
ethylene glycol
pH 8.0, 30°C, recombinant enzyme, uncompetitive mode
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
the enzyme is involved in the branched-chain amino acid biosynthesis pathway
metabolism
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the enzyme catalyzes the first common step in biosynthesis of branched-chain amino acids isoleucine, leucine and valine
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
structure-function relationship, effects of ligand, Mg2+ and NADPH, binding on the enzyme conformation, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
enzyme KARI in complex with Mg2+ or with Mg2+ and NADPH, hanging-drop method by vaporphase diffusion at 18°C, 0.003 ml of protein solution containing 6 mg/ml enzyme, 50 mM Hepes, pH 7.5, 5 mM NADPH, and 5 mM MgCl2, is mixed with 0.001 ml of reservoir solution containing 0.2 M magnesium chloride hexahydrate, 0.1 M Tris-HCl, pH 8.5, and 15% w/v PEG 4000, a few days to 3 months, X-ray diffraction structure determination and analysis at 1.55 A and 2.80 A resolution, respectively, molecular replacement
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
recombinant His-tagged enzyme from Escherichia coli strain BL21(DE3) by affinity chromatography
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
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the enzyme is a promising target for the design of herbicides
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lee, Y.; Ta, H.T.; Duggleby, R.G.
Cyclopropane-1,1-dicarboxylate is a slow-, tight-binding inhibitor of rice ketol-acid reductoisomerase
Plant Sci.
168
1035-1040
2005
Oryza sativa (Q65XK0)
Wang, B.; Li, Z.; Li, Y.; Wang, S.
Syntheses and biological activities of ethyl N-hydroxy-N-(substituted)phenyloxamates as KARI inhibitors
Chem. Res. Chin. Univ.
23
280-283
2007
Oryza sativa
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Wang, B.; Li, Y.; Wang, J.; Ma, Y.; Li, Z.
Molecular design, synthesis and biological activities of amidines as new ketol-acid reductoisomerase inhibitors
Chin. Chem. Lett.
19
651-654
2008
Escherichia coli, Oryza sativa, Spinacia oleracea
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Liu, X.H.; Zhang, C.Y.; Guo, W.C.; Li, Y.H.; Chen, P.Q.; Wang, T.; Dong, W.L.; Wang, B.L.; Sun, H.W.; Li, Z.M.
Synthesis, bioactivity and SAR study of N-(5-substituted-1,3,4-thiadiazol-2-yl)-N-cyclopropylformyl-thioureas as ketol-acid reductoisomerase inhibitors
J. Enzyme Inhib. Med. Chem.
24
545-552
2009
Oryza sativa
Leung, E.W.; Guddat, L.W.
Conformational changes in a plant ketol-acid reductoisomerase upon Mg2+ and NADPH binding as revealed by two crystal structures
J. Mol. Biol.
389
167-182
2009
Oryza sativa (Q65XK0), Oryza sativa
Liu, X.H.; Chen, P.Q.; Wang, B.L.; Dong, W.L.; Li, Y.H.; Xie, X.Q.; Li, Z.M.
High throughput receptor-based virtual screening under ZINC database, synthesis, and biological evaluation of ketol-acid reductoisomerase inhibitors
Chem. Biol. Drug Des.
75
228-232
2010
Oryza sativa
Wang, B.; Ma, Y.; Li, Y.; Wang, S.; Li, Z.
The design, synthesis of amide KARI inhibitors and their biological activities
Front. Chem.
4
186-190
2009
Brassica rapa subsp. oleifera, Echinochloa crus-galli, Oryza sativa
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