DB code: D00012

CATH domain	3.40.50.720 : Rossmann fold	Catalytic domain
CATH 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)
1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2	D00007 D00603 T00002 T00227
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

CATH domain

Related DB codes (homologues)

1.10.1040.10 : N-(1-d-carboxylethyl)-l-norvaline Dehydrogenase; domain 2

D00007 D00603 T00002 T00227

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

Uniprot Enzyme Name
UniprotKB	Protein name	Synonyms	Pfam
Q01292	Ketol-acid reductoisomerase, chloroplastic	EC 1.1.1.86 Acetohydroxy-acid reductoisomerase Alpha-keto-beta-hydroxylacil 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	(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.	Tetramer of similar but non-identical chains.	Plastid, chloroplast.	Magnesium.

KEGG Pathways
Map code	Pathways	E.C.
MAP00290	Valine, leucine and isoleucine biosynthesis
MAP00770	Pantothenate and CoA 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 18420	18409 18409	16474 16474	15378 15378	15684 15684	18009 18009
PubChem	888 888	440878 440878	5884 5884	1038 1038	440279 440279	5886 5886

1qmgA01	Unbound	Unbound	Unbound		Unbound	Analogue:APX	Unbound
1qmgB01	Unbound	Unbound	Unbound		Unbound	Analogue:APX	Unbound
1qmgC01	Unbound	Unbound	Unbound		Unbound	Analogue:APX	Unbound
1qmgD01	Unbound	Unbound	Unbound		Unbound	Analogue:APX	Unbound
1yveI01	Unbound	Unbound	Bound:NDP		Unbound	Unbound	Unbound
1yveJ01	Unbound	Unbound	Bound:NDP		Unbound	Unbound	Unbound
1yveK01	Unbound	Unbound	Bound:NDP		Unbound	Unbound	Unbound
1yveL01	Unbound	Unbound	Bound:NDP		Unbound	Unbound	Unbound
1qmgA02	Analogue:2x_MN	Unbound	Unbound		Analogue:DMV	Unbound	Unbound
1qmgB02	Analogue:2x_MN	Unbound	Unbound		Analogue:DMV	Unbound	Unbound
1qmgC02	Analogue:2x_MN	Unbound	Unbound		Analogue:DMV	Unbound	Unbound
1qmgD02	Analogue:2x_MN	Unbound	Unbound		Analogue:DMV	Unbound	Unbound
1yveI02	Bound:2x_MG	Unbound	Unbound		Unbound	Unbound	Intermediate-analogue:_MG-HIO
1yveJ02	Bound:2x_MG	Unbound	Unbound		Unbound	Unbound	Intermediate-analogue:_MG-HIO
1yveK02	Bound:2x_MG	Unbound	Unbound		Unbound	Unbound	Intermediate-analogue:_MG-HIO
1yveL02	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	HIS 226
1qmgB01	HIS 226
1qmgC01	HIS 226
1qmgD01	HIS 226
1yveI01	HIS 226
1yveJ01	HIS 226
1yveK01	HIS 226
1yveL01	HIS 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
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