Ligand 2,3-dihydroxyisovalerate

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Basic Ligand Information

Molecular Structure

Picture of 2,3-dihydroxyisovalerate (click for magnification)

Molecular Formula

BRENDA Name

InChIKey

C₅H₁₀O₄

2,3-dihydroxyisovalerate

CDHXXEKDLLJPCM-KHVQSSSXSA-N

Synonyms:

2,3-dihydroxy-3-isovalerate, 2,3-dihydroxy-3-methyl-butanoate, 2,3-Dihydroxy-3-methylbutanoate, 2,3-dihydroxy-3-methylbutanoic acid, 2,3-dihydroxy-3-methylbutyrate, 2,3-Dihydroxy-isovalerate, alpha,beta-dihydroxyisovalerate, D,L-2,3-dihydroxy-isovalerate, DL-2,3-dihydroxyisovalerate

Pathway Source

Pathways

BRENDA

valine metabolism

Show all BRENDA pathways known for 2,3-dihydroxyisovalerate

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Roles as Enzyme Ligand

In Vivo Substrate in Enzyme-catalyzed Reactions (5 results)

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EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

4.2.1.9

2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O

713917, 715798, 732214, 758969

4.2.1.9

2,3-dihydroxy-isovalerate = 2-oxoisovalerate

699075

4.2.1.9

2,3-dihydroxyisovalerate = 2-oxovalerate + H2O

700277

4.2.1.9

2,3-dihydroxyisovalerate = ?

33959, 33984, 33965, 33983, 33960, 33981

4.2.1.9

DL-2,3-dihydroxyisovalerate = 2-oxo-isovalerate + H2O

713840

4.2.1.9

5 entries

In Vivo Product in Enzyme-catalyzed Reactions (3 results)

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EC NUMBER

PROVEN IN VIVO REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxy-3-methylbutanoate + NADP+

639169, 639172, 639174, 639170, 639175, 639177, 639178, 639183, 639187, 33969, 639171, 639180, 639176, 639179, 639181, 639182, 639184, 639185, 639186

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxy-3-methylbutanoate + NADP+ + H+

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxyisovalerate + NADP+

1.1.1.86

3 entries

Substrate in Enzyme-catalyzed Reactions (9 results)

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EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

4.2.1.9

2,3-dihydroxy-3-methylbutanoate = 2-oxoisovalerate + H2O

33968, 33974, 33964, 33959, 33962, 33971, 33973, 33975, 33976, 33977, 33978, 33979, 33980, 33982, 33984, 33969, 33961, 33963, 33965, 33967, 33960, 33972, 33981, 33985, 33966, 33983, 33970

4.2.1.9

2,3-dihydroxy-3-methylbutanoate = 3-methyl-2-oxobutanoate + H2O

732214, 758969, 713917, 715798

4.2.1.9

2,3-dihydroxy-isovalerate = 2-oxoisovalerate

699075

4.2.1.9

2,3-dihydroxyisovalerate = 2-oxoisovalerate + H2O

746896

4.2.1.9

2,3-dihydroxyisovalerate = 2-oxovalerate + H2O

700277

4.2.1.9

2,3-dihydroxyisovalerate = ?

33959, 33984, 33965, 33983, 680539, 33960, 33981

4.2.1.9

D,L-2,3-dihydroxy-isovalerate = ?

696105

4.2.1.9

DL-2,3-dihydroxyisovalerate = 2-oxo-isovalerate + H2O

713840

4.2.1.9

DL-2,3-dihydroxyisovalerate = ?

716148

4.2.1.9

9 entries

Product in Enzyme-catalyzed Reactions (12 results)

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EC NUMBER

REACTION

REACTION DIAGRAM

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.383

(S)-2-acetolactate + NADH + H+ = 2,3-dihydroxy-3-methylbutanoate + NAD+

1.1.1.383

(S)-2-acetolactate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

1.1.1.86

3-hydroxy-3-methyl-2-oxobutanoate + NADPH + H+ = 2,3-dihydroxy-3-methyl-butanoate + NADP+

1.1.1.86

(S)-2-acetolactate + NADH + H+ = 2,3-dihydroxy-3-methylbutanoate + NAD+

1.1.1.86

(S)-2-acetolactate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

1.1.1.86

2-acetolactate + NADH + H+ = 2,3-dihydroxy-3-methylbutanoate + NAD+ + H+

1.1.1.86

2-acetolactate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxy-3-methylbutanoate + NADP+

, 639169, 639172, 639174, 639170, 639175, 639177, 639178, 639183, 639187, 33969, 639171, 639180, 639176, 639179, 639181, 639182, 639184, 639185, 639186

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxy-3-methylbutanoate + NADP+ + H+

1.1.1.86

3-hydroxy-3-methyl-2-oxobutanoate + NADPH + H+ = 2,3-dihydroxy-3-methylbutanoate + NADP+

1.1.1.86

2-acetolactate + NADPH = 2,3-dihydroxyisovalerate + NADP+

1.1.1.86

NADPH + 2-oxo-3-hydroxyisovalerate = NADP+ + alpha,beta-dihydroxyisovalerate

Inhibitor in Enzyme-catalyzed Reactions (3 results)

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EC NUMBER

COMMENTARY

LITERATURE

ENZYME 3D STRUCTURE

1.1.1.86

639179

1.1.1.86

linear noncompetitive inhibitor of both 2-acetolactate and NADPH

Enzyme Kinetic Parameters

k_cat Value (Turnover Number) (6 results)

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EC NUMBER

TURNOVER NUMBER [1/S]

TURNOVER NUMBER MAXIMUM [1/S]

COMMENTARY

LITERATURE

1.1.1.86

0.00417

pH 7.4, 25°C

639177

4.2.1.9

0.31

pH 7, 50°C, enzyme activated by 2-mercaptoethanol

732214

4.2.1.9

0.31

pH 7, 50°C, non-activated enzyme

11.5

75.8

K_M Value (11 results)

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EC NUMBER

KM VALUE [MM]

KM VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

4.2.1.9

0.54

680539

4.2.1.9

0.85

mitochondrial enzyme

0.97

1.03

supernatant enzyme

1.5

1.5

pH 8.0, Tris buffer, since only one of the isomers present in the racemic substrate is active, the corrected Km would be 0.75 mM

2.1

pH 7, 50°C

732214

4.2.1.9

2.7

pH 7.0, 30°C

2.8

3.7

pH 8.0, temperature not specified in the publication

716148

4.2.1.9

11 entries

K_i Value (4 results)

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EC NUMBER

KI VALUE [MM]

KI VALUE MAXIMUM [MM]

COMMENTARY

LITERATURE

1.1.1.86

0.095

pH 8.2, 30°C, (2S)-2-acetolactate as variable substrate, 0.250 mM NADPH as fixed substrate

639179

1.1.1.86

0.145

pH 8.2, 30°C, (2S)-2-aceto-2-hydroxybutanoate as variable substrate, 0.250 mM NADPH as fixed substrate

639179

1.1.1.86

0.935

pH 8.2, 30°C, NADPH as variable substrate, 0.2 mM (2S)-2-acetolactate as fixed substrate

639179

1.1.1.86

1.5

pH 8.2, 30°C, NADPH as variable substrate, 0.2 mM (2S)-2-aceto-2-hydroxybutanoate as fixed substrate

639179

1.1.1.86

4 entries

References & Links

Literature References (56)

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BRENDA REFERENCE ID

PUBMED ID

TITLE

YEAR

AUTHORS

JOURNAL

VOLUME

PAGES

33959

13727223

Dihydroxy acid dehydrase: an enzyme involved in the biosynthesis of isoleucine and valine

1961

Myers, J.W.

J. Biol. Chem.

236

1414-1418

33960

13962154

Studies in valine biosynthesis. V. Characteristics of the purified dihydroxyacid dehydratase from spinach leaves

1963

Kanamori, M.; Wixom, R.L.

J. Biol. Chem.

238

998-1005

33961

4986563

Purification and properties of dihydroxy acid dehydratase from soluble and mitochondrial fractions of Neurospora crassa

1970

Altmiller, D.H.; Wagner, R.P.

Arch. Biochem. Biophys.

138

160-170

33962

4933736

A rapid determination of dihydroxyacid dehydratase activity in microbial cell suspensions

1971

Wixom, R.L.; Garrett, J.L.; Fetzek, J.P.

Anal. Biochem.

262-274

33963

alpha,beta-Dihydroxy acid dehydratase (Neurospora crassa and spinach)

1970

Kiritani, K.; Wagner, R.P.

Methods Enzymol.

17A

755-764

33964

5003668

Studies in valine biosynthesis. IX. The enzymes in photosynthetic and autotrophic bacteria

1971

Wixom, R.L.; Heinemann, M.A.; Semeraro, R.J.; Joseph, A.A.

Biochim. Biophys. Acta

244

532-546

33965

4259051

Separation of mitochondrial membranes of Neurospora crassa. II. Submitochondrial localization of the isoleucine-valine biosynthetic pathway

1972

Cassady, W.E.; Leiter, E.H.; Bergquist, A.; Wagner, R.P.

J. Cell Biol.

66-72

33966

4669215

Enzymes of the isoleucine-valine pathway in Acinetobacter

1972

Twarog, R.

J. Bacteriol.

111

37-46

33967

4264553

Neurospora mutants with mitochondria deficient in dihydroxy acid dehydratase. Properties of dihydroxy acid dehydratase from mutant strain 332

1972

Altmiller, D.H.

Biochem. Biophys. Res. Commun.

1000-1006

33968

Stereochemistry of the reductoisomerase and alpha,beta-dihydroxyacid dehydratase-catalysed steps in valine and isoleucine biosynthesis. Observation of a novel tertiary ketol rearrangement

1974

Armstrong, F.B.

J. Chem. Soc. Chem. Commun.

1974

351-352

33969

4616942

Subcellular localization of isoleucine-valine biosynthetic enzymes in yeast

1974

Ryan, E.D.; Kohlhaw, G.B.

J. Bacteriol.

120

631-637

33970

328058

Stereoselectivity and stereospecificity of the alpha,beta-dihydroxyacid dehydratase from Salmonella typhimurium

1977

Armstrong, F.B.; Muller, U.S.; Reary, J.B.; Whitehouse, D.; Crout, D.H.G.

Biochim. Biophys. Acta

498

282-293

33971

367373

Dihydroxyacid dehydratase: the site of hyperbaric oxygen poisoning in branch-chain amino acid biosynthesis

1978

Brown, O.R.; Yein, F.

Biochem. Biophys. Res. Commun.

1219-1224

33972

2831190

Dihydroxy acid dehydratase from spinach contains a [2Fe-2S] cluster

1988

Flint, D.H.; Emptage, M.H.

J. Biol. Chem.

263

3558-3564

33973

2445227

An activity stain for dihydroxy-acid dehydratase

1987

Kuo, C.F.; Mashino, T.; Fridovich, I.

Anal. Biochem.

164

526-530

33974

Structure-activity studies with alpha,beta-dihydroxyacid dehydratase of Salmonella typhimurium

1985

Armstrong, F.B.; Lipscomb, E.L.; Crout, D.H.G.; Morgan, P.J.

J. Chem. Soc. Perkin Trans.

691-696

33975

8226748

The inactivation of Fe-S cluster containing hydro-lyases by superoxide

1993

Flint, D.H.; Tuminello, J.F.; Emptage, M.H.

J. Biol. Chem.

268

22369-22376

33976

8325851

The role and properties of the iron-sulfur cluster in Escherichia coli dihydroxy-acid dehydratase

1993

Flint, D.H.; Emptage, M.H.; Finnegan, M.G.; Fu, W.; Johnson, M.K.

J. Biol. Chem.

268

14732-14742

33977

8244991

The inactivation of dihydroxy-acid dehydratase in Escherichia coli treated with hyperbaric oxygen occurs because of the destruction of its Fe-S cluster, but the enzyme remains in the cell in a form that can be reactivated

1993

Flint, D.H.; Smyk-Randall, E.; Tuminello, J.F.; Draczynska-Lusiak, B.; Brown, O.R.

J. Biol. Chem.

268

25547-25552

33978

7630323

Quantitative effects of redox-cycling chemicals on the oxidant-sensitive enzyme dihydroxy-acid dehydratase

1995

Babu, B.N.; Brown, O.R.

Microbios

157-170

33979

1394687

Bacteriostatic effect of 4,7-dicyanobenzofurazan due to inactivation of 2,3-dihydroxyisovalerate dehydratase

1992

Takabatake, T.; Hasegawa, M.; Nagano, T.; Hirobe, M.

Chem. Pharm. Bull.

1644-1646

33980

Isolation and characterization of oxygen sensitive mutants of Escherichia coli

1992

Matsumura, Y.; Imanaka, T.

J. Ferment. Bioeng.

262-266

33981

7648198

Conversion of aldonic acids to their corresponding 2-keto-3-deoxy-analogs by the non-carbohydrate enzyme dihydroxy acid dehydratase (DHAD)

1995

Limberg, G.; Klaffke, W.; Thiem, J.

Bioorg. Med. Chem.

487-494

33982

8663055

Studies on the synthesis of the Fe-S cluster of dihydroxy-acid dehydratase in escherichia coli crude extract. Isolation of O-acetylserine sulfhydrylases A and B and beta-cystathionase based on their ability to mobilize sulfur from cysteine and to participate in Fe-S cluster synthesis

1996

Flint, D.H.; Tuminello, J.F.; Miller, T.J.

J. Biol. Chem.

271

16053-16067

33983

2002010

Characterization of enzymes of the branched-chain amino acid biosynthetic pathway in Methanococcus spp

1991

Xing, R.; Whitman, W.B.

J. Bacteriol.

173

2086-2092

33984

3314584

A reverse-phase high-performance liquid chromatography assay for dihydroxy-acid dehydratase

1987

Smyk-Randall, E.M.; Brown, O.R.

Anal. Biochem.

164

434-438

33985

Mechanism and stereochemistry of alpha,beta-dihydroxyacid dehydratase

1991

Pirrung, M.C.; Holmes, C.P.; Horowitz, D.M.; Nunn, D.S.

J. Am. Chem. Soc.

113

1020-1025

639169

4388025

Purification and properties of the acetohydroxy acid isomeroreductase of Salmonella typhimurium

1969

Arfin, S.M.; Umbarger, H.E.

J. Biol. Chem.

244

1118-1127

639170

5866387

Biosynthesis of valine and isoleucine in plants. 3. Reductoisomerase of Phaseolus radiatus

1965

Satyanarayana, T.; Radhakrishnan, A.N.

Biochim. Biophys. Acta

110

380-388

639171

The reductoisomerase of Neurospora crassa

1966

Kiritani, K.; Narise, S.; Wagner, R.P.

J. Biol. Chem.

241

2047-2051

639172

4147080

A kinetic study of alpha-acetohydroxy acid isomeroreductase from Salmonella typhimurium

1973

Shematek, E.M.; Arfin, S.M.; Diven, W.F.

Arch. Biochem. Biophys.

158

132-138

639174

803501

The subunit structure of alpha-acetohydroxyacid isomeroreductase from Salmonella typhimurium

1975

Hofler, J.G.; Decedue, C.J.; Luginbuhl, G.H.; Reynolds, J.A.; Burns, R.O.

J. Biol. Chem.

250

877-882

639175

2653423

Mechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement

1989

Chunduru, S.K.; Mrachko, G.T.; Calvo, K.C.

Biochemistry

486-493

639176

2590180

Purification and characterization of acetohydroxyacid reductoisomerase from spinach chloroplasts

1989

Dumas, R.; Joyard, J.; Douce, R.

Biochem. J.

262

971-976

639177

2189496

Oxalyl hydroxamates as reaction-intermediate analogues for ketol-acid reductoisomerase

1990

Aulabaugh, A.; Schloss, J.V.

Biochemistry

2824-2830

639178

1567200

The pH dependence of the kinetic parameters of ketol acid reductoisomerase indicates a proton shuttle mechanism for alkyl migration

1992

Mrachko, G.T.; Chunduru, S.K.; Calvo, K.C.

Arch. Biochem. Biophys.

294

446-453

639179

Isolation and kinetic properties of acetohydroxy acid isomeroreductase from spinach (Spinacia oleracea) chloroplasts overexpressed in Escherichia coli

1992

Dumas, R.; Job, D.; Ortholand, J.Y.; Emeric, G.; Greiner, A.; Douce, R.

Biochem. J.

288

865-874

639180

12231988

Ketol-acid reductoisomerase from barley (Hordeum vulgare). Purification, properties, and specific inhibition

1993

Durner, J.; Knoerzer, O.C.; Boeger, P.

Plant Physiol.

103

903-910

639181

Interactions of plant acetohydroxy acid isomeroreductase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects

1994

Dumas, R.; Cornillon-Bertrand, C.; Guigue-Talet, P.; Genix, P.; Douce, R.; Job, D.

Biochem. J.

301

813-820

639182

9218783

The crystal structure of plant acetohydroxy acid isomeroreductase complexed with NADPH, two magnesium ions and a herbicidal transition state analog determined at 1.65 A resolution

1997

Biou, V.; Dumas, R.; Cohen-Addad, C.; Douce, R.; Job, D.; Pebay-Peyroula, E.

EMBO J.

3405-3415

639183

9015391

Reversal of the nucleotide specificity of ketol acid reductoisomerase by site-directed mutagenesis identifies the NADPH binding site

1997

Rane, M.J.; Calvo, K.C.

Arch. Biochem. Biophys.

338

83-89

639184

9187358

Purification and characterization of a fusion protein of plant acetohydroxy acid synthase and acetohydroxy acid isomeroreductase

1997

Dumas, R.; Biou, V.; Douce, R.

FEBS Lett.

408

156-160

639185

9737852

A loop deletion in the plant acetohydroxy acid isomeroreductase homodimer generates an active monomer with reduced stability and altered magnesium affinity

1998

Wessel, P.M.; Biou, V.; Douce, R.; Dumas, R.

Biochemistry

12753-12760

639186

Structure of spinach acetohydroxyacid isomeroreductase complexed with its reaction product dihydroxymethylvalerate, manganese and (phospho)-ADP-ribose

2000

Thomazeau, K.; Dumas, R.; Halgand, F.; Forest, E.; Douce, R.; Biou, V.

Acta Crystallogr. Sect. D

389-397

639187

11352718

Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase

2001

Dumas, R.; Biou, V.; Halgand, F.; Douce, R.; Duggleby, R.G.

Acc. Chem. Res.

399-408

680539

16567425

Catalytic promiscuity in dihydroxy-acid dehydratase from the thermoacidophilic archaeon Sulfolobus solfataricus

2006

Kim, S.; Lee, S.B.

J. Biochem.

139

591-596

696105

18945212

Reactivity of nitric oxide with the [4Fe-4S] cluster of dihydroxyacid dehydratase from Escherichia coli

2009

Duan, X.; Yang, J.; Ren, B.; Tan, G.; Ding, H.

Biochem. J.

417

783-789

699075

19121344

Metabolic engineering of the L-valine biosynthesis pathway in Corynebacterium glutamicum using promoter activity modulation

2009

Holatko, J.; Elisakova, V.; Prouza, M.; Sobotka, M.; Nesvera, J.; Patek, M.

J. Biotechnol.

139

203-210

700277

18811727

Nitric oxide-induced bacteriostasis and modification of iron-sulphur proteins in Escherichia coli

2008

Ren, B.; Zhang, N.; Yang, J.; Ding, H.

Mol. Microbiol.

953-964

713840

20935122

Metabolic engineering of Corynebacterium glutamicum for 2-ketoisovalerate production

2010

Krause, F.S.; Blombach, B.; Eikmanns, B.J.

Appl. Environ. Microbiol.

8053-8061

713917

21533914

Engineering Bacillus subtilis for isobutanol production by heterologous Ehrlich pathway construction and the biosynthetic 2-ketoisovalerate precursor pathway overexpression

2011

Li, S.; Wen, J.; Jia, X.

Appl. Microbiol. Biotechnol.

577-589

715798

20364396

Factors enhancing L-valine production by the growth-limited L-isoleucine auxotrophic strain Corynebacterium glutamicum DeltailvA DeltapanB ilvNM13 (pECKAilvBNC)

2010

Denina, I.; Paegle, L.; Prouza, M.; Holatko, J.; Patek, M.; Nesvera, J.; Ruklisha, M.

J. Ind. Microbiol. Biotechnol.

689-699

716148

20864475

Downregulation of Rv0189c, encoding a dihydroxyacid dehydratase, affects growth of Mycobacterium tuberculosis in vitro and in mice

2011

Singh, V.; Chandra, D.; Srivastava, B.S.; Srivastava, R.

Microbiology

157

38-46

732214

26102631

Characterization of recombinantly expressed dihydroxy-acid dehydratase from Sulfobus solfataricus - a key enzyme for the conversion of carbohydrates into chemicals

2015

Carsten, J.M.; Philipp, A.; Sieber, V.

J. Biotechnol.

211

31-41

746896

25081555

Characterization and modification of enzymes in the 2-ketoisovalerate biosynthesis pathway of Ralstonia eutropha H16

2015

Lu, J.; Brigham, C.J.; Plassmeier, J.K.; Sinskey, A.J.

Appl. Microbiol. Biotechnol.

761-774