DB code: D00012

CATH domain 3.40.50.720 : Rossmann fold Catalytic domain
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 Catalytic domain
E.C. 1.1.1.86
CSA 1yve
M-CSA 1yve
MACiE

CATH domain Related DB codes (homologues)
3.40.50.720 : Rossmann fold S00543 S00551 S00552 S00553 S00602 S00604 S00605 S00608 S00610 S00625 S00319 S00328 S00329 S00330 S00331 S00332 D00456 D00457 D00458 S00324 S00320 S00325 S00326 S00327 D00459 S00335 S00336 S00334 T00219 S00339 D00513 D00001 D00002 D00003 D00005 D00007 D00008 D00010 D00017 D00018 D00023 D00027 D00028 D00031 D00032 D00033 D00034 D00035 D00037 D00048 D00071 D00476 D00481 D00482 D00490 D00492 D00494 D00545 D00601 D00603 D00604 D00605 D00615 D00845 D00857 D00858 M00161 M00171 M00210 T00002 T00010 T00011 T00015 T00227 T00247 T00408 T00414 D00827 D00262 D00274 D00275 M00035 T00109
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2 D00007 D00603 T00002 T00227

Uniprot Enzyme Name
UniprotKB Protein name Synonyms Pfam
Q01292 Ketol-acid reductoisomerase, chloroplastic
EC 1.1.1.86
Acetohydroxy-acid reductoisomerase
Alpha-keto-beta-hydroxylacyl reductoisomerase
PF01450 (IlvC)
PF07991 (IlvN)
[Graphical View]

KEGG enzyme name
ketol-acid reductoisomerase
dihydroxyisovalerate dehydrogenase (isomerizing)
acetohydroxy acid isomeroreductase
ketol acid reductoisomerase
alpha-keto-beta-hydroxylacyl reductoisomerase
2-hydroxy-3-keto acid reductoisomerase
acetohydroxy acid reductoisomerase
acetolactate reductoisomerase
dihydroxyisovalerate (isomerizing) dehydrogenase
isomeroreductase
reductoisomerase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q01292 ILV5_SPIOL (2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH. (R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH. Tetramer of similar but non-identical chains. Plastid, chloroplast. Magnesium.

KEGG Pathways
Map code Pathways E.C.
MAP00770 Pantothenate and CoA biosynthesis
MAP00290 Valine, leucine and isoleucine biosynthesis

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C06010 C00005 C00080 C04272 C00006
E.C.
Compound Magnesium (S)-2-Hydroxy-2-methyl-3-oxobutanoate NADPH H+ (R)-2,3-Dihydroxy-3-methylbutanoate NADP+
Type divalent metal (Ca2+, Mg2+) carbohydrate,carboxyl group amide group,amine group,nucleotide others carbohydrate,carboxyl group amide group,amine group,nucleotide
ChEBI 18420
18409
16474
15378
15684
18009
PubChem 888
440878
5884
1038
440279
5886
1qmgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:APX Unbound
1qmgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:APX Unbound
1qmgC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:APX Unbound
1qmgD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Analogue:APX Unbound
1yveI01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NDP Unbound Unbound Unbound
1yveJ01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NDP Unbound Unbound Unbound
1yveK01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NDP Unbound Unbound Unbound
1yveL01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Bound:NDP Unbound Unbound Unbound
1qmgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Unbound Unbound Analogue:DMV Unbound Unbound
1qmgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Unbound Unbound Analogue:DMV Unbound Unbound
1qmgC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Unbound Unbound Analogue:DMV Unbound Unbound
1qmgD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Analogue:2x_MN Unbound Unbound Analogue:DMV Unbound Unbound
1yveI02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound Intermediate-analogue:_MG-HIO
1yveJ02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound Intermediate-analogue:_MG-HIO
1yveK02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound Intermediate-analogue:_MG-HIO
1yveL02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:2x_MG Unbound Unbound Unbound Unbound Intermediate-analogue:_MG-HIO

Reference for Active-site residues
resource references E.C.
PDB;1qmg, 1yve & Swiss-prot;Q01292

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1qmgA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1qmgB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1qmgC01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1qmgD01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1yveI01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1yveJ01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1yveK01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1yveL01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain HIS 226
1qmgA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1qmgB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1qmgC02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1qmgD02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1yveI02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1yveJ02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1yveK02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)
1yveL02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 315;GLU 319(Magnesium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
Fig.4
[4]
SCHEME I, p.453
[11]
Fig.1, Scheme 1, p.6034
[16]
p.3411-3413
[20]
p.6032-6033
[23]
p.395, Fig.5
[24]
Fig.6, p.407

References
[1]
Resource
Comments
Medline ID
PubMed ID 6401279
Journal J Bacteriol
Year 1983
Volume 153
Pages 259-69
Authors Primerano DA, Burns RO
Title Role of acetohydroxy acid isomeroreductase in biosynthesis of pantothenic acid in Salmonella typhimurium.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 2653423
Journal Biochemistry
Year 1989
Volume 28
Pages 486-93
Authors Chunduru SK, Mrachko GT, Calvo KC
Title Mechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2189496
Journal Biochemistry
Year 1990
Volume 29
Pages 2824-30
Authors Aulabaugh A, Schloss JV
Title Oxalyl hydroxamates as reaction-intermediate analogues for ketol-acid reductoisomerase.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 1567200
Journal Arch Biochem Biophys
Year 1992
Volume 294
Pages 446-53
Authors Mrachko GT, Chunduru SK, Calvo KC
Title The pH dependence of the kinetic parameters of ketol acid reductoisomerase indicates a proton shuttle mechanism for alkyl migration.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 8379936
Journal Biochem J
Year 1993
Volume 294
Pages 821-8
Authors Dumas R, Curien G, DeRose RT, Douce R
Title Branched-chain-amino-acid biosynthesis in plants: molecular cloning and characterization of the gene encoding acetohydroxy acid isomeroreductase (ketol-acid reductoisomerase) from Arabidopsis thaliana (thale cress).
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 8173081
Journal DNA Seq
Year 1993
Volume 4
Pages 95-103
Authors Inui M, Vertes AA, Kobayashi M, Kurusu Y, Yukawa H
Title Identification and sequence determination of the acetohydroxy acid isomeroreductase gene from Brevibacterium flavum MJ233.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8366043
Journal J Bacteriol
Year 1993
Volume 175
Pages 5595-603
Authors Keilhauer C, Eggeling L, Sahm H
Title Isoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 12231988
Journal Plant Physiol
Year 1993
Volume 103
Pages 903-910
Authors Durner J, Knorzer OC, Boger P
Title Ketol-Acid Reductoisomerase from Barley (Hordeum vulgare) (Purification, Properties, and Specific Inhibition).
Related PDB
Related UniProtKB
[9]
Resource
Comments
Medline ID
PubMed ID 8053906
Journal Biochem J
Year 1994
Volume 301
Pages 813-20
Authors Dumas R, Cornillon-Bertrand C, Guigue-Talet P, Genix P, Douce R, Job D
Title Interactions of plant acetohydroxy acid isomeroreductase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 7932712
Journal J Mol Biol
Year 1994
Volume 242
Pages 578-81
Authors Dumas R, Job D, Douce R, Pebay-Peyroula E, Cohen-Addad C
Title Crystallization and preliminary crystallographic data for acetohydroxy acid isomeroreductase from Spinacia oleracea.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 7742305
Journal Biochemistry
Year 1995
Volume 34
Pages 6026-36
Authors Dumas R, Butikofer MC, Job D, Douce R
Title Evidence for two catalytically different magnesium-binding sites in acetohydroxy acid isomeroreductase by site-directed mutagenesis.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 8529876
Journal Gene
Year 1995
Volume 166
Pages 127-32
Authors De Rossi E, Leva R, Gusberti L, Manachini PL, Riccardi G
Title Cloning, sequencing and expression of the ilvBNC gene cluster from Streptomyces avermitilis.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 8921849
Journal Gene
Year 1996
Volume 177
Pages 83-5
Authors Gusberti L, Cantoni R, De Rossi E, Branzoni M, Riccardi G
Title Cloning and sequencing of the ilvBNC gene cluster from Mycobacterium avium.
Related PDB
Related UniProtKB
[14]
Resource
Comments
Medline ID
PubMed ID 8576056
Journal J Bacteriol
Year 1996
Volume 178
Pages 1187-96
Authors Epelbaum S, Chipman DM, Barak Z
Title Metabolic effects of inhibitors of two enzymes of the branched-chain amino acid pathway in Salmonella typhimurium.
Related PDB
Related UniProtKB
[15]
Resource
Comments
Medline ID
PubMed ID 9015391
Journal Arch Biochem Biophys
Year 1997
Volume 338
Pages 83-9
Authors Rane MJ, Calvo KC
Title Reversal of the nucleotide specificity of ketol acid reductoisomerase by site-directed mutagenesis identifies the NADPH binding site.
Related PDB
Related UniProtKB
[16]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
Medline ID
PubMed ID 9218783
Journal EMBO J
Year 1997
Volume 16
Pages 3405-15
Authors Biou V, Dumas R, Cohen-Addad C, Douce R, Job D, Pebay-Peyroula E
Title 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.
Related PDB 1yve
Related UniProtKB Q01292
[17]
Resource
Comments
Medline ID
PubMed ID 9537993
Journal Biochemistry
Year 1998
Volume 37
Pages 4773-81
Authors Halgand F, Vives F, Dumas R, Biou V, Andersen J, Andrieu JP, Cantegril R, Gagnon J, Douce R, Forest E, Job D
Title Kinetic and mass spectrometric analyses of the interactions between plant acetohydroxy acid isomeroreductase and thiadiazole derivatives.
Related PDB
Related UniProtKB
[18]
Resource
Comments
Medline ID
PubMed ID 9737852
Journal Biochemistry
Year 1998
Volume 37
Pages 12753-60
Authors Wessel PM, Biou V, Douce R, Dumas R
Title A loop deletion in the plant acetohydroxy acid isomeroreductase homodimer generates an active monomer with reduced stability and altered magnesium affinity.
Related PDB
Related UniProtKB
[19]
Resource
Comments
Medline ID
PubMed ID 9818746
Journal J Antimicrob Chemother
Year 1998
Volume 42
Pages 475-82
Authors Grandoni JA, Marta PT, Schloss JV
Title Inhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents.
Related PDB
Related UniProtKB
[20]
Resource
Comments
Medline ID
PubMed ID 10320328
Journal Biochemistry
Year 1999
Volume 38
Pages 6025-34
Authors Halgand F, Dumas R, Biou V, Andrieu JP, Thomazeau K, Gagnon J, Douce R, Forest E
Title Characterization of the conformational changes of acetohydroxy acid isomeroreductase induced by the binding of Mg2+ ions, NADPH, and a competitive inhibitor.
Related PDB
Related UniProtKB
[21]
Resource
Comments
Medline ID
PubMed ID 9914514
Journal Eur J Biochem
Year 1999
Volume 259
Pages 356-9
Authors Laprevote O, Serani L, Das BC, Halgand F, Forest E, Dumas R
Title Stepwise building of a 115-kDa macromolecular edifice monitored by electrospray mass spectrometry. The case of acetohydroxy acid isomeroreductase.
Related PDB
Related UniProtKB
[22]
Resource
Comments
Medline ID
PubMed ID 10024470
Journal Protein Expr Purif
Year 1999
Volume 15
Pages 57-61
Authors Hill CM, Duggleby RG
Title Purified recombinant Escherichia coli ketol-acid reductoisomerase is unsuitable for use in a coupled assay of acetohydroxyacid synthase activity due to an unexpected side reaction.
Related PDB
Related UniProtKB
[23]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 72-595.
Medline ID
PubMed ID 10739911
Journal Acta Crystallogr D Biol Crystallogr
Year 2000
Volume 56
Pages 389-97
Authors Thomazeau K, Dumas R, Halgand F, Forest E, Douce R, Biou V
Title Structure of spinach acetohydroxyacid isomeroreductase complexed with its reaction product dihydroxymethylvalerate, manganese and (phospho)-ADP-ribose.
Related PDB 1qmg
Related UniProtKB Q01292
[24]
Resource
Comments
Medline ID
PubMed ID 11352718
Journal Acc Chem Res
Year 2001
Volume 34
Pages 399-408
Authors Dumas R, Biou V, Halgand F, Douce R, Duggleby RG
Title Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase.
Related PDB
Related UniProtKB
[25]
Resource
Comments
Medline ID
PubMed ID 12136009
Journal Genetics
Year 2002
Volume 161
Pages 1043-52
Authors Bateman JM, Perlman PS, Butow RA
Title Mutational bisection of the mitochondrial DNA stability and amino acid biosynthetic functions of ilv5p of budding yeast.
Related PDB
Related UniProtKB

Comments
This enzyme catalyzes two successive reactions:
(A) Isomerization (composed of two reactions, eliminative double-bond formation & addition to double-bond).
(B) Hydride transfer from NADPH.

Created Updated
2004-03-24 2009-02-26