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Information on EC 4.2.1.9 - dihydroxy-acid dehydratase
for references in articles please use BRENDA:EC4.2.1.9
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The enzyme appears in viruses and cellular organisms
- 4.2.1.9
-
branched-chain
-
dhads
- fe-s
- acetolactate
-
isomeroreductase
- isobutanol
- 2-ketoisovalerate
- reductoisomerase
- 2,3-butanediol
-
bcaas
-
ketol-acid
-
ilvbncd
- drug development
- analysis
- synthesis
showSynonyms
dihydroxy-acid dehydratase, dihydroxyacid dehydratase, dihydroxy acid dehydratase, afilv3a, ssdhad, 2,3-dihydroxyisovalerate dehydratase, dihydroxy acid dehydrase, more
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SYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
2,3-dihydroxy acid hydrolyase
-
-
-
-
2,3-dihydroxyisovalerate dehydratase
-
-
-
-
acetohydroxyacid dehydratase
-
-
-
-
alpha,beta-dihydroxy acid dehydratase
-
-
-
-
alpha,beta-dihydroxyisovalerate dehydratase
-
-
-
-
DAD
-
-
-
-
dehydratase, dihydroxy acid
-
-
-
-
DHAD
dihydroxy acid dehydrase
-
-
-
-
dihydroxy acid dehydratase
dihydroxyacid dehydratase
IlvD
SsDHAD
VEG110
-
-
-
-
Vegetative protein 110
-
-
-
-
DHAD
-
-
-
-
dihydroxy acid dehydratase
-
-
-
-
dihydroxyacid dehydratase
-
-
-
-
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O
stereochemistry, elimination and protonation steps are stereospecific, enol-keto conversion takes place with proton addition at C-3 to the same face of the enol as that of the departing hydroxy-group
-
2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O
polar but concerted elimination mechanism which should proceed through an anti transition state
-
2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O
-
-
-
-
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
elimination
-
-
-
-
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PATHWAY SOURCE
PATHWAYS
KEGG
MetaCyc
L-isoleucine biosynthesis I (from threonine), L-isoleucine biosynthesis II, L-isoleucine biosynthesis III, L-isoleucine biosynthesis IV, L-valine biosynthesis, pyruvate fermentation to isobutanol (engineered)
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SYSTEMATIC NAME
IUBMB Comments
2,3-dihydroxy-3-methylbutanoate hydro-lyase (3-methyl-2-oxobutanoate-forming)
-
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CAS REGISTRY NUMBER
COMMENTARY
9024-32-2
-
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
(+)-2,3-dihydroxy-3-ethylpentanoate
?
-
Substrates: 20% of the activity with 2,3-dihydroxyisovalerate
Products: -
Products: -
?
(2R,3R)-2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
(2R,3S)-2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylvalerate
3-methyl-2-oxovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-isovalerate
2-oxoisovalerate
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxyisovalerate
2-oxoisovalerate + H2O
Substrates: -
Products: -
Products: -
?
2,3-dihydroxyisovalerate
2-oxovalerate + H2O
-
Substrates: IlvD, an iron-sulfur enzyme, catalyses the conversion from 2,3-dihydroxyisovalerate to 2-keto-isovalerate and is essential for the branchend-chain amino acid biosynthesis
Products: -
Products: -
?
D-gluconate
2-keto-3-deoxygluconate + H2O
Substrates: -
Products: -
Products: -
?
DL-2,3-dihydroxyisovalerate
2-oxo-isovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
threo-2,3-dihydroxybutanoate
?
-
Substrates: at 45% of the activity with 2,3-dihydroxyisovalerate
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
Chromatium sp.
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: no activity with 2S-2,3-dihydroxy-3-methylbutanoate
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: 2R-2,3-dihydroxy-3-methylbutanoate
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
2-oxoisovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
-
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. alpha-ketoisovalerate
Products: i.e. alpha-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. alpha-ketoisovalerate
Products: i.e. alpha-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: the enzyme is implicated in latex metabolism
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: biosynthesis pathway of the branched chain amino acids valine and isoleucine
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: biosynthesis pathway of the branched chain amino acids valine and isoleucine
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
Chromatium sp.
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: 2R,3R-(2,3)-dihydroxy-3-methylpentanoate, at 45% of the activity with 2,3-dihydroxyisovalerate
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: 2R,3R-dihydroxy-3-methylpentanoate, 2R,3S-dihydroxy-3-methylpentanoate, no activity with isomers with 2S configuration
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
3-methyl-2-oxopentanoate + H2O
-
Substrates: 2R,3S-2,3-dihydroxy-3-methylpentanoate, 2R,3R-2,3-dihydroxy-3-methylpentanoate
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
?
-
Substrates: 2R,3R-(2,3)-dihydroxy-3-methylpentanoate
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
?
-
Substrates: involved in synthesis of Ile
Products: -
Products: -
?
2,3-dihydroxyisovalerate
?
-
Substrates: involved in biosynthesis of Val
Products: -
Products: -
?
D-gluconate
2-dehydro-3-deoxy-D-gluconate + H2O
Substrates: -
Products: -
Products: -
?
D-gluconate
2-dehydro-3-deoxy-D-gluconate + H2O
Substrates: -
Products: -
Products: -
?
D-glycerate
pyruvate + H2O
Substrates: the enzyme catalyzes the non-natural dehydration of D-glycerate to pyruvate
Products: -
Products: -
?
D-glycerate
pyruvate + H2O
Substrates: the enzyme catalyzes the non-natural dehydration of D-glycerate to pyruvate
Products: -
Products: -
?
additional information
?
-
Substrates: reaction product determination by formation of 2,4-dinitrophenylhydrazone from the keto acid product resulting in 2-ketoisovalerate-dinitrophenylhydrazone
Products: -
Products: -
?
additional information
?
-
-
Substrates: reaction product determination by formation of 2,4-dinitrophenylhydrazone from the keto acid product resulting in 2-ketoisovalerate-dinitrophenylhydrazone
Products: -
Products: -
?
additional information
?
-
Substrates: reaction product determination by formation of 2,4-dinitrophenylhydrazone from the keto acid product resulting in 2-ketoisovalerate-dinitrophenylhydrazone
Products: -
Products: -
?
additional information
?
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
-
Substrates: third enzyme in the branched-chain amino acid biosynthetic pathway
Products: -
Products: -
?
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
LITERATURE
COMMENTARY
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2,3-dihydroxy-3-methylvalerate
3-methyl-2-oxovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-isovalerate
2-oxoisovalerate
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxyisovalerate
2-oxovalerate + H2O
-
Substrates: IlvD, an iron-sulfur enzyme, catalyses the conversion from 2,3-dihydroxyisovalerate to 2-keto-isovalerate and is essential for the branchend-chain amino acid biosynthesis
Products: -
Products: -
?
DL-2,3-dihydroxyisovalerate
2-oxo-isovalerate + H2O
-
Substrates: -
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
-
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: -
Products: i.e. 2-ketoisovalerate
Products: i.e. 2-ketoisovalerate
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: the enzyme is implicated in latex metabolism
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: biosynthesis pathway of the branched chain amino acids valine and isoleucine
Products: -
Products: -
?
2,3-dihydroxy-3-methylbutanoate
3-methyl-2-oxobutanoate + H2O
Substrates: biosynthesis pathway of the branched chain amino acids valine and isoleucine
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
?
-
Substrates: 2R,3R-(2,3)-dihydroxy-3-methylpentanoate
Products: -
Products: -
?
2,3-dihydroxy-3-methylpentanoate
?
-
Substrates: involved in synthesis of Ile
Products: -
Products: -
?
2,3-dihydroxyisovalerate
?
-
Substrates: involved in biosynthesis of Val
Products: -
Products: -
?
additional information
?
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
Substrates: dihydroxy-acid dehydratase is one of the key enzymes involved in the biosynthetic pathway of the branched chain amino acids
Products: -
Products: -
?
additional information
?
-
-
Substrates: third enzyme in the branched-chain amino acid biosynthetic pathway
Products: -
Products: -
?
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COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
[2Fe-2S]-center
DHAD can accommodate [Fe2S2] and [Fe4S4] clusters. Only the [Fe2S2] cluster-bound form is catalytically active. The [Fe2S2] cluster is coordinated by at least one non-cysteinyl ligand, which can be replaced by the thiol group(s) of dithiothreitol. [Fe2S2] cluster-containing NFU2 protein is likely the physiological cluster donor for in vivo maturation of DHAD
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METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
Co2+
Fe2+
Iron
Mg2+
Mn2+
Ni2+
-
divalent cation required. Mg2+, Mn2+, Ni2+, Co2+, and Fe2+ are nearly equally effective
Co2+
-
divalent cation required. Mg2+, Mn2+, Ni2+, Co2+, and Fe2+ are nearly equally effective
Fe2+
-
divalent cation required. Mg2+, Mn2+, Ni2+, Co2+, and Fe2+ are nearly equally effective
Iron
-
contains a [4Fe-4S]2+,+ cluster which is essential for catalysis and unstable in the presence of O2 and O2-
Mg2+
-
divalent cation required. Mg2+, Mn2+, Ni2+, Co2+, and Fe2+ are nearly equally effective
Mn2+
-
divalent cation required. Mg2+, Mn2+, Ni2+, Co2+, and Fe2+ are nearly equally effective
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INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
(NH4)2Fe(SO4)2
10 mM, 50°C, 45% loss of activity, dehydration of D-gluconate
3-(5-nitrofuran-2-yl)-5,6-dihydroimidazo[2,1-b][1,3]thiazole hydrochloride
-
-
4,7-dicyanobenzofurazan
-
bacteriostatic effect due to inactivation of 2,3-dihydroxyisovalerate dehydratase
BaCl2
100 mM, 50°C, 43% loss of activity, dehydration of D-gluconate
CaCl2
10 mM, 50°C, 77% loss of activity, dehydration of D-gluconate
CuSO4
10 mM, 50°C, 86% loss of activity, dehydration of D-gluconate
D-glycerate
competitive. Presence of 20 mM D-glycerate decreases catalytic activity towards D-gluconate drastically to 5% residual activity
imidazole
leads to a complete elimination of enzyme activity towards D-gluconate
nitric oxide
-
nitric oxide halts bacterial growth via inhibition of the branched-chain amino acid biosynthesis enzyme dihydroxyacid dehydratase
ZnCl2
10 mM, 50°C, 95% loss of activity, dehydration of D-gluconate
additional information
-
formation of the IlvD-bound DNIC, dinitrosyl-iron complex, and inactivation of the enzyme activity under anaerobic conditions, reaction kinetics of NO and enzyme using diethylamine NONOate as NO donor. GSH fails to prevent the NO-mediated modification of the IlvD [4Fe-4S] cluster regardless of the presence of O2 in the medium, overview
-
NO
-
IlvD is completely inactivated in cells by NO with the concomitant formation of the IlvD-bound dinitrosyl iron complex, DNIC. While the IlvD-bound DNIC and other protein-bound DNICs are stable in cells under anaerobic growth conditions, they are efficiently repaired under aerobic growth conditions even without new protein synthesis, L-cysteine plays an important role, overview
NO
-
inactivation of Rv0189c by NO probably inhibits bacterial growth
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ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2-mercaptoethanol
increases activity up to 3fold. Activation modulates thermotolerance at 50°C
additional information
heat activation: the heat treatment step in purification at 80°C increases the total activity about 2.5 to 3-fold and the specific activity about 20 to 30-fold
-
additional information
-
heat activation: the heat treatment step in purification at 80°C increases the total activity about 2.5 to 3-fold and the specific activity about 20 to 30-fold
-
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DISEASE
TITLE OF PUBLICATION
LINK TO PUBMED
Infections
The Aspergillus fumigatus dihydroxyacid dehydratase Ilv3A/IlvC is required for full virulence.
Mycoses
The Aspergillus fumigatus dihydroxyacid dehydratase Ilv3A/IlvC is required for full virulence.
Tuberculosis
Rv0189c encodes dihydroxyacid dehydratase: Down-regulation affects growth of Mycobacterium tuberculosis in vitro and in mice.