EzCatDB: D00012
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DB codeD00012
CATH domainDomain 13.40.50.720 : Rossmann foldCatalytic domain
Domain 21.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2Catalytic domain
E.C.1.1.1.86
CSA1yve

CATH domainRelated DB codes (homologues)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2D00007,D00603,T00002,T00227
3.40.50.720 : Rossmann foldS00543,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

Enzyme Name
UniProtKBKEGG

Q01292
Protein nameKetol-acid reductoisomerase, chloroplasticketol-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
SynonymsEC 1.1.1.86
Acetohydroxy-acid reductoisomerase
Alpha-keto-beta-hydroxylacil reductoisomerase
PfamPF01450 (IlvC)
PF07991 (IlvN)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00290Valine, leucine and isoleucine biosynthesis
MAP00770Pantothenate and CoA biosynthesis

UniProtKB:Accession NumberQ01292
Entry nameILV5_SPIOL
Activity(R)-2,3-dihydroxy-3-methylbutanoate + NADP(+) = (S)-2-hydroxy-2-methyl-3-oxobutanoate + NADPH.,(2R,3R)-2,3-dihydroxy-3-methylpentanoate + NADP(+) = (S)-2-hydroxy-2-ethyl-3-oxobutanoate + NADPH.
SubunitTetramer of similar but non-identical chains.
Subcellular locationPlastid, chloroplast.
CofactorMagnesium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00305C06010C00005C00080C04272C00006
CompoundMagnesium(S)-2-Hydroxy-2-methyl-3-oxobutanoateNADPHH+(R)-2,3-Dihydroxy-3-methylbutanoateNADP+
Typedivalent metal (Ca2+, Mg2+)carbohydrate,carboxyl groupamide group,amine group,nucleotideotherscarbohydrate,carboxyl groupamide group,amine group,nucleotide
ChEBI18420
18409
16474
15378
15684
18009

PubChem888
440878
5884
1038
440279
5886

               
1qmgA01UnboundUnboundUnbound UnboundAnalogue:APXUnbound
1qmgB01UnboundUnboundUnbound UnboundAnalogue:APXUnbound
1qmgC01UnboundUnboundUnbound UnboundAnalogue:APXUnbound
1qmgD01UnboundUnboundUnbound UnboundAnalogue:APXUnbound
1yveI01UnboundUnboundBound:NDP UnboundUnboundUnbound
1yveJ01UnboundUnboundBound:NDP UnboundUnboundUnbound
1yveK01UnboundUnboundBound:NDP UnboundUnboundUnbound
1yveL01UnboundUnboundBound:NDP UnboundUnboundUnbound
1qmgA02Analogue:2x_MNUnboundUnbound Analogue:DMVUnboundUnbound
1qmgB02Analogue:2x_MNUnboundUnbound Analogue:DMVUnboundUnbound
1qmgC02Analogue:2x_MNUnboundUnbound Analogue:DMVUnboundUnbound
1qmgD02Analogue:2x_MNUnboundUnbound Analogue:DMVUnboundUnbound
1yveI02Bound:2x_MGUnboundUnbound UnboundUnboundIntermediate-analogue:_MG-HIO
1yveJ02Bound:2x_MGUnboundUnbound UnboundUnboundIntermediate-analogue:_MG-HIO
1yveK02Bound:2x_MGUnboundUnbound UnboundUnboundIntermediate-analogue:_MG-HIO
1yveL02Bound:2x_MGUnboundUnbound UnboundUnboundIntermediate-analogue:_MG-HIO

Active-site residues
resource
PDB;1qmg, 1yve & Swiss-prot;Q01292
pdbCatalytic residuesCofactor-binding residues
          
1qmgA01HIS 226
 
1qmgB01HIS 226
 
1qmgC01HIS 226
 
1qmgD01HIS 226
 
1yveI01HIS 226
 
1yveJ01HIS 226
 
1yveK01HIS 226
 
1yveL01HIS 226
 
1qmgA02 
ASP 315;GLU 319(Magnesium binding)
1qmgB02 
ASP 315;GLU 319(Magnesium binding)
1qmgC02 
ASP 315;GLU 319(Magnesium binding)
1qmgD02 
ASP 315;GLU 319(Magnesium binding)
1yveI02 
ASP 315;GLU 319(Magnesium binding)
1yveJ02 
ASP 315;GLU 319(Magnesium binding)
1yveK02 
ASP 315;GLU 319(Magnesium binding)
1yveL02 
ASP 315;GLU 319(Magnesium binding)

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID6401279
JournalJ Bacteriol
Year1983
Volume153
Pages259-69
AuthorsPrimerano DA, Burns RO
TitleRole of acetohydroxy acid isomeroreductase in biosynthesis of pantothenic acid in Salmonella typhimurium.
[2]
PubMed ID2653423
JournalBiochemistry
Year1989
Volume28
Pages486-93
AuthorsChunduru SK, Mrachko GT, Calvo KC
TitleMechanism of ketol acid reductoisomerase--steady-state analysis and metal ion requirement.
[3]
PubMed ID2189496
JournalBiochemistry
Year1990
Volume29
Pages2824-30
AuthorsAulabaugh A, Schloss JV
TitleOxalyl hydroxamates as reaction-intermediate analogues for ketol-acid reductoisomerase.
[4]
PubMed ID1567200
JournalArch Biochem Biophys
Year1992
Volume294
Pages446-53
AuthorsMrachko GT, Chunduru SK, Calvo KC
TitleThe pH dependence of the kinetic parameters of ketol acid reductoisomerase indicates a proton shuttle mechanism for alkyl migration.
[5]
PubMed ID8379936
JournalBiochem J
Year1993
Volume294
Pages821-8
AuthorsDumas R, Curien G, DeRose RT, Douce R
TitleBranched-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).
[6]
PubMed ID8173081
JournalDNA Seq
Year1993
Volume4
Pages95-103
AuthorsInui M, Vertes AA, Kobayashi M, Kurusu Y, Yukawa H
TitleIdentification and sequence determination of the acetohydroxy acid isomeroreductase gene from Brevibacterium flavum MJ233.
[7]
PubMed ID8366043
JournalJ Bacteriol
Year1993
Volume175
Pages5595-603
AuthorsKeilhauer C, Eggeling L, Sahm H
TitleIsoleucine synthesis in Corynebacterium glutamicum: molecular analysis of the ilvB-ilvN-ilvC operon.
[8]
PubMed ID12231988
JournalPlant Physiol
Year1993
Volume103
Pages903-910
AuthorsDurner J, Knorzer OC, Boger P
TitleKetol-Acid Reductoisomerase from Barley (Hordeum vulgare) (Purification, Properties, and Specific Inhibition).
[9]
PubMed ID8053906
JournalBiochem J
Year1994
Volume301
Pages813-20
AuthorsDumas R, Cornillon-Bertrand C, Guigue-Talet P, Genix P, Douce R, Job D
TitleInteractions of plant acetohydroxy acid isomeroreductase with reaction intermediate analogues: correlation of the slow, competitive, inhibition kinetics of enzyme activity and herbicidal effects.
[10]
PubMed ID7932712
JournalJ Mol Biol
Year1994
Volume242
Pages578-81
AuthorsDumas R, Job D, Douce R, Pebay-Peyroula E, Cohen-Addad C
TitleCrystallization and preliminary crystallographic data for acetohydroxy acid isomeroreductase from Spinacia oleracea.
[11]
PubMed ID7742305
JournalBiochemistry
Year1995
Volume34
Pages6026-36
AuthorsDumas R, Butikofer MC, Job D, Douce R
TitleEvidence for two catalytically different magnesium-binding sites in acetohydroxy acid isomeroreductase by site-directed mutagenesis.
[12]
PubMed ID8529876
JournalGene
Year1995
Volume166
Pages127-32
AuthorsDe Rossi E, Leva R, Gusberti L, Manachini PL, Riccardi G
TitleCloning, sequencing and expression of the ilvBNC gene cluster from Streptomyces avermitilis.
[13]
PubMed ID8921849
JournalGene
Year1996
Volume177
Pages83-5
AuthorsGusberti L, Cantoni R, De Rossi E, Branzoni M, Riccardi G
TitleCloning and sequencing of the ilvBNC gene cluster from Mycobacterium avium.
[14]
PubMed ID8576056
JournalJ Bacteriol
Year1996
Volume178
Pages1187-96
AuthorsEpelbaum S, Chipman DM, Barak Z
TitleMetabolic effects of inhibitors of two enzymes of the branched-chain amino acid pathway in Salmonella typhimurium.
[15]
PubMed ID9015391
JournalArch Biochem Biophys
Year1997
Volume338
Pages83-9
AuthorsRane MJ, Calvo KC
TitleReversal of the nucleotide specificity of ketol acid reductoisomerase by site-directed mutagenesis identifies the NADPH binding site.
[16]
CommentsX-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS).
PubMed ID9218783
JournalEMBO J
Year1997
Volume16
Pages3405-15
AuthorsBiou V, Dumas R, Cohen-Addad C, Douce R, Job D, Pebay-Peyroula E
TitleThe 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 PDB1yve
Related UniProtKBQ01292
[17]
PubMed ID9537993
JournalBiochemistry
Year1998
Volume37
Pages4773-81
AuthorsHalgand F, Vives F, Dumas R, Biou V, Andersen J, Andrieu JP, Cantegril R, Gagnon J, Douce R, Forest E, Job D
TitleKinetic and mass spectrometric analyses of the interactions between plant acetohydroxy acid isomeroreductase and thiadiazole derivatives.
[18]
PubMed ID9737852
JournalBiochemistry
Year1998
Volume37
Pages12753-60
AuthorsWessel PM, Biou V, Douce R, Dumas R
TitleA loop deletion in the plant acetohydroxy acid isomeroreductase homodimer generates an active monomer with reduced stability and altered magnesium affinity.
[19]
PubMed ID9818746
JournalJ Antimicrob Chemother
Year1998
Volume42
Pages475-82
AuthorsGrandoni JA, Marta PT, Schloss JV
TitleInhibitors of branched-chain amino acid biosynthesis as potential antituberculosis agents.
[20]
PubMed ID10320328
JournalBiochemistry
Year1999
Volume38
Pages6025-34
AuthorsHalgand F, Dumas R, Biou V, Andrieu JP, Thomazeau K, Gagnon J, Douce R, Forest E
TitleCharacterization of the conformational changes of acetohydroxy acid isomeroreductase induced by the binding of Mg2+ ions, NADPH, and a competitive inhibitor.
[21]
PubMed ID9914514
JournalEur J Biochem
Year1999
Volume259
Pages356-9
AuthorsLaprevote O, Serani L, Das BC, Halgand F, Forest E, Dumas R
TitleStepwise building of a 115-kDa macromolecular edifice monitored by electrospray mass spectrometry. The case of acetohydroxy acid isomeroreductase.
[22]
PubMed ID10024470
JournalProtein Expr Purif
Year1999
Volume15
Pages57-61
AuthorsHill CM, Duggleby RG
TitlePurified recombinant Escherichia coli ketol-acid reductoisomerase is unsuitable for use in a coupled assay of acetohydroxyacid synthase activity due to an unexpected side reaction.
[23]
CommentsX-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 72-595.
PubMed ID10739911
JournalActa Crystallogr D Biol Crystallogr
Year2000
Volume56
Pages389-97
AuthorsThomazeau K, Dumas R, Halgand F, Forest E, Douce R, Biou V
TitleStructure of spinach acetohydroxyacid isomeroreductase complexed with its reaction product dihydroxymethylvalerate, manganese and (phospho)-ADP-ribose.
Related PDB1qmg
Related UniProtKBQ01292
[24]
PubMed ID11352718
JournalAcc Chem Res
Year2001
Volume34
Pages399-408
AuthorsDumas R, Biou V, Halgand F, Douce R, Duggleby RG
TitleEnzymology, structure, and dynamics of acetohydroxy acid isomeroreductase.
[25]
PubMed ID12136009
JournalGenetics
Year2002
Volume161
Pages1043-52
AuthorsBateman JM, Perlman PS, Butow RA
TitleMutational bisection of the mitochondrial DNA stability and amino acid biosynthetic functions of ilv5p of budding yeast.

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.

createdupdated
2004-03-242009-02-26


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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
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Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
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Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
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