EzCatDB: S00417
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DB codeS00417
CATH domainDomain 13.40.718.10 : Isopropylmalate DehydrogenaseCatalytic domain
E.C.1.1.1.85
CSA1a05

CATH domainRelated DB codes (homologues)
3.40.718.10 : Isopropylmalate DehydrogenaseS00416

Enzyme Name
UniProtKBKEGG

P12010P61495Q56268
Protein name3-isopropylmalate dehydrogenase3-isopropylmalate dehydrogenase3-isopropylmalate dehydrogenase3-isopropylmalate dehydrogenase
beta-isopropylmalic enzyme
beta-isopropylmalate dehydrogenase
threo-Ds-3-isopropylmalate dehydrogenase
3-carboxy-2-hydroxy-4-methylpentanoate:NAD+ oxidoreductase
SynonymsEC 1.1.1.85
Beta-IPM dehydrogenase
IMDH
3-IPM-DH
EC 1.1.1.85
Beta-IPM dehydrogenase
IMDH
3-IPM-DH
EC 1.1.1.85
Beta-IPM dehydrogenase
IMDH
3-IPM-DH
PfamPF00180 (Iso_dh)
[Graphical view]
PF00180 (Iso_dh)
[Graphical view]
PF00180 (Iso_dh)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00290Valine, leucine and isoleucine biosynthesis

UniProtKB:Accession NumberP12010P61495Q56268
Entry nameLEU3_BACCOLEU3_THETHLEU3_THIFE
Activity(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl- 2-oxopentanoate + CO(2) + NADH.(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl- 2-oxopentanoate + CO(2) + NADH.(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl- 2-oxopentanoate + CO(2) + NADH.
SubunitHomodimer.Homodimer.Homodimer.
Subcellular locationCytoplasm.Cytoplasm.Cytoplasm.
CofactorBinds 1 magnesium or manganese ion per subunit.Binds 1 magnesium or manganese ion per subunit.Binds 1 magnesium or ion per subunit.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C04411C00003C04236C00004C00233C00011
CompoundMagnesium3-IsopropylmalateNAD+3-Carboxy-4-methyl-2-oxopentanoateNADH4-Methyl-2-oxopentanoateCO2
Typedivalent metal (Ca2+, Mg2+)carbohydrate,carboxyl groupamide group,amine group,nucleotidecarbohydrate,carboxyl groupamide group,amine group,nucleotidecarbohydrate,carboxyl groupothers
ChEBI18420
43468
15846
1467
16908
48430
16526
PubChem888
5462261
5893
5462259
439153
70
280
               
1a05ABound:_MGBound:IPMUnboundUnboundUnboundUnboundUnbound
1a05BBound:_MGBound:IPMUnboundUnboundUnboundUnboundUnbound
1ayqAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ayqBUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dpzAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dpzBUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dr0AUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dr0BUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dr8AUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dr8BUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1g2uAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1gc8AUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1gc8BUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1gc9AUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1hexAUnboundUnboundBound:NADUnboundUnboundUnboundUnbound
1idmAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ipdAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osiAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osiBUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osiCUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osiDUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osjAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1osjBUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1xaaAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1xabAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1xacAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1xadAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2ayqAUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2ayqBUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [5], [12] & [15]
pdbCatalytic residuesCofactor-binding residuescomment
           
1a05ATYR  140;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 
1a05BTYR  140;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 
1ayqATYR  141;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 
1ayqBTYR  141;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 
1dpzATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1dpzBTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1dr0ATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1dr0BTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1dr8ATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1dr8BTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1g2uATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant A172V
1gc8ATYR 1139;LYS 1185;ASP 1217
ASP 1217;ASP 1241;ASP 1245(Magnesium binding)
mutant A1172F
1gc8BTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant A172F
1gc9ATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant A172G
1hexATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1idmATYR  137;LYS  183;ASP  215
ASP  215;ASP  239;ASP  243(Magnesium binding)
mutant R82;K83
1ipdATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1osiATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1osiBTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1osiCTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1osiDTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1osjATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant A172L
1osjBTYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1xaaATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1xabATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
 
1xacATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant S82R
1xadATYR  139;LYS  185;ASP  217
ASP  217;ASP  241;ASP  245(Magnesium binding)
mutant S82R
2ayqATYR  141;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 
2ayqBTYR  141;LYS  190;ASP  222
ASP  222;ASP  246;ASP  250(Magnesium binding)
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Fig.7, p.8675-8676
[7]

[9]Fig.1
[15]p.2164-2165
[26]p.976-980

references
[1]
PubMed ID3069841
JournalJ Biochem (Tokyo)
Year1988
Volume104
Pages679-80
AuthorsKatsube Y, Tanaka N, Takenaka A, Yamada T, Oshima T
TitleCrystallization and preliminary X-ray data for 3-isopropylmalate dehydrogenase of Thermus thermophilus.
[2]
CommentsX-ray crystallography
PubMed ID2277037
JournalJ Biochem (Tokyo)
Year1990
Volume108
Pages449-56
AuthorsYamada T, Akutsu N, Miyazaki K, Kakinuma K, Yoshida M, Oshima T
TitlePurification, catalytic properties, and thermal stability of threo-Ds-3-isopropylmalate dehydrogenase coded by leuB gene from an extreme thermophile, Thermus thermophilus strain HB8.
[3]
PubMed ID1901851
JournalJ Biochem (Tokyo)
Year1991
Volume109
Pages1-2
AuthorsOnodera K, Moriyama H, Takenaka A, Tanaka N, Akutsu N, Muro M, Oshima T, Imada K, Sato M, Katsube Y
TitleCrystallization and preliminary X-ray studies of a Bacillus subtilis and Thermus thermophilus HB8 chimeric 3-isopropylmalate dehydrogenase.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID92085286
PubMed ID1748999
JournalJ Mol Biol
Year1991
Volume222
Pages725-38
AuthorsImada K, Sato M, Tanaka N, Katsube Y, Matsuura Y, Oshima T
TitleThree-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2 A resolution.
Related PDB1ipd
Related UniProtKBP61495
[5]
CommentsHomologous enzyme
PubMed ID1888729
JournalBiochemistry
Year1991
Volume30
Pages8671-8
AuthorsHurley JH, Dean AM, Koshland DE Jr, Stroud RM
TitleCatalytic mechanism of NADP(+)-dependent isocitrate dehydrogenase: implications from the structures of magnesium-isocitrate and NADP+ complexes.
[6]
PubMed ID1400259
JournalJ Biochem (Tokyo)
Year1992
Volume112
Pages173-4
AuthorsSakurai M, Onodera K, Moriyama H, Matsumoto O, Tanaka N, Numata K, Imada K, Sato M, Katsube Y, Oshima T
TitleCrystallization and preliminary X-ray studies of a Bacillus subtilis and Thermus thermophilus HB8 chimeric 3-isopropylmalate dehydrogenase and thermostable mutants of it.
[7]
PubMed ID8405446
JournalFEBS Lett
Year1993
Volume332
Pages37-8
AuthorsMiyazaki K, Oshima T
TitleTyr-139 in Thermus thermophilus 3-isopropylmalate dehydrogenase is involved in catalytic function.
[8]
PubMed ID8029202
JournalProtein Eng
Year1994
Volume7
Pages453-9
AuthorsOnodera K, Sakurai M, Moriyama H, Tanaka N, Numata K, Oshima T, Sato M, Katsube Y
TitleThree-dimensional structures of chimeric enzymes between Bacillus subtilis and Thermus thermophilus 3-isopropylmalate dehydrogenases.
[9]
CommentsX-ray crystallography
PubMed ID7881901
JournalStructure
Year1994
Volume2
Pages1007-16
AuthorsHurley JH, Dean AM
TitleStructure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity.
Related PDB1hex
[10]
PubMed ID8140100
JournalProtein Eng
Year1994
Volume7
Pages99-102
AuthorsMiyazaki K, Kadono S, Sakurai M, Moriyama H, Tanaka N, Oshima T
TitleChemical modification and site-directed mutagenesis of Tyr36 of 3-isopropylmalate dehydrogenase from Thermus thermophilus HB8.
[11]
PubMed ID7590327
JournalGene
Year1995
Volume164
Pages85-7
AuthorsKryger G, Wallon G, Lovett ST, Ringe D, Petsko GA
TitleRevision of the amino-acid sequence of 3-isopropylmalate dehydrogenase from Salmonella typhimurium by means of X-ray crystallography.
[12]
PubMed ID8576088
JournalJ Biochem (Tokyo)
Year1995
Volume118
Pages745-52
AuthorsKadono S, Sakurai M, Moriyama H, Sato M, Hayashi Y, Oshima T, Tanaka N
TitleLigand-induced changes in the conformation of 3-isopropylmalate dehydrogenase from Thermus thermophilus.
[13]
PubMed ID7608131
JournalJ Biochem (Tokyo)
Year1995
Volume117
Pages408-13
AuthorsMoriyama H, Onodera K, Sakurai M, Tanaka N, Kirino-Kagawa H, Oshima T, Katsube Y
TitleThe crystal structures of mutated 3-isopropylmalate dehydrogenase from Thermus thermophilus HB8 and their relationship to the thermostability of the enzyme.
[14]
PubMed ID8637845
JournalProtein Eng
Year1995
Volume8
Pages763-7
AuthorsSakurai M, Moriyama H, Onodera K, Kadono S, Numata K, Hayashi Y, Kawaguchi J, Yamagishi A, Oshima T, Tanaka N
TitleThe crystal structure of thermostable mutants of chimeric 3-isopropylmalate dehydrogenase, 2T2M6T.
Related PDB1xac,1xad
[15]
PubMed ID8535253
JournalProtein Sci
Year1995
Volume4
Pages2156-67
AuthorsDean AM, Dvorak L
TitleThe role of glutamate 87 in the kinetic mechanism of Thermus thermophilus isopropylmalate dehydrogenase.
[16]
PubMed ID7773180
JournalProtein Sci
Year1995
Volume4
Pages84-92
AuthorsZhang T, Koshland DE Jr
TitleModeling substrate binding in Thermus thermophilus isopropylmalate dehydrogenase.
[17]
CommentsX-ray crystallography
JournalActa Crystallogr D Biol Crystallogr
Year1996
Volume52
Pages124-8
AuthorsSakurai M, Ohzeki M, Miyazaki K, Moriyama H, Sato M, Tanaka N, Oshima T
TitleStructure of a loop-deleted variant of 3-isopropylmalate dehydrogenase from Thermus thermophilus: An internal reprieve tolerance mechanism.
Related PDB1idm
[18]
PubMed ID8875643
JournalProtein Eng
Year1996
Volume9
Pages663-70
AuthorsMagyar C, Szilagyi A, Zavodszky P
TitleRelationship between thermal stability and 3-D structure in a homology model of 3-isopropylmalate dehydrogenase from Escherichia coli.
[19]
PubMed ID15299625
JournalActa Crystallogr D Biol Crystallogr
Year1996
Volume52
Pages623-30
AuthorsNagata C
TitleCryocrystallography of 3-Isopropylmalate Dehydrogenase from Thermus thermophilus and its Chimeric Enzyme.
Related PDB1xaa,1xab
[20]
CommentsX-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS)
Medline ID98158316
PubMed ID9498551
JournalJ Biochem (Tokyo)
Year1997
Volume122
Pages1092-104
AuthorsTsuchiya D, Sekiguchi T, Takenaka A
TitleCrystal structure of 3-isopropylmalate dehydrogenase from the moderate facultative thermophile, Bacillus coagulans: two strategies for thermostabilization of protein structures.
Related PDB1ayq,2ayq
Related UniProtKBP12010
[21]
CommentsX-RAY CRYSTALLOGRAPHY (2.27 ANGSTROMS)
Medline ID97240818
PubMed ID9086278
JournalJ Mol Biol
Year1997
Volume266
Pages1016-31
AuthorsWallon G, Kryger G, Lovett ST, Oshima T, Ringe D, Petsko GA
TitleCrystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus.
Related UniProtKBP61495
[22]
CommentsX-ray crystallography
PubMed ID9051733
JournalProtein Eng
Year1997
Volume10
Pages45-52
AuthorsQu C, Akanuma S, Moriyama H, Tanaka N, Oshima T
TitleA mutation at the interface between domains causes rearrangement of domains in 3-isopropylmalate dehydrogenase.
Related PDB1osi,1osj
[23]
PubMed ID9278279
JournalProtein Eng
Year1997
Volume10
Pages665-72
AuthorsWallon G, Lovett ST, Magyar C, Svingor A, Szilagyi A, Zavodszky P, Ringe D, Petsko GA
TitleSequence and homology model of 3-isopropylmalate dehydrogenase from the psychrotrophic bacterium Vibrio sp. I5 suggest reasons for thermal instability.
[24]
PubMed ID9761923
JournalActa Crystallogr D Biol Crystallogr
Year1998
Volume54
Pages444-5
AuthorsSuzuki T, Moriyama H, Hirose R, Sakurai M, Tanaka N, Oshima T
TitleCrystallization and preliminary X-ray studies on the hyperstable 3-isopropylmalate dehydrogenase from the thermoacidophilic archaeon Sulfolobus sp. strain 7.
[25]
PubMed ID9636162
JournalProc Natl Acad Sci U S A
Year1998
Volume95
Pages7406-11
AuthorsZavodszky P, Kardos J, Svingor, Petsko GA
TitleAdjustment of conformational flexibility is a key event in the thermal adaptation of proteins.
[26]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS)
Medline ID98416693
PubMed ID9739088
JournalStructure
Year1998
Volume6
Pages971-82
AuthorsImada K, Inagaki K, Matsunami H, Kawaguchi H, Tanaka H, Tanaka N, Namba K
TitleStructure of 3-isopropylmalate dehydrogenase in complex with 3-isopropylmalate at 2.0 A resolution: the role of Glu88 in the unique substrate-recognition mechanism.
Related PDB1a05
Related UniProtKBQ56268
[27]
PubMed ID10683439
JournalFEBS Lett
Year2000
Volume468
Pages48-52
AuthorsNemeth A, Svingor A, Pocsik M, Dobo J, Magyar C, Szilagyi A, Gal P, Zavodszky P
TitleMirror image mutations reveal the significance of an intersubunit ion cluster in the stability of 3-isopropylmalate dehydrogenase.
[28]
PubMed ID10989439
JournalMethods Enzymol
Year2000
Volume324
Pages301-22
AuthorsHayashi-Iwasaki Y, Oshima T
TitlePurification and characterization of recombinant 3-isopropylmalate dehydrogenases from Thermus thermophilus and other microorganisms.
[29]
PubMed ID10964981
JournalProtein Eng
Year2000
Volume13
Pages527-33
AuthorsHori T, Moriyama H, Kawaguchi J, Hayashi-Iwasaki Y, Oshima T, Tanaka N
TitleThe initial step of the thermal unfolding of 3-isopropylmalate dehydrogenase detected by the temperature-jump Laue method.
[30]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS)
Medline ID20272095
PubMed ID10810156
JournalProtein Eng
Year2000
Volume13
Pages253-8
AuthorsNurachman Z, Akanuma S, Sato T, Oshima T, Tanaka N
TitleCrystal structures of 3-isopropylmalate dehydrogenases with mutations at the C-terminus: crystallographic analyses of structure-stability relationships.
Related PDB1dpz,1dr0,1dr8
Related UniProtKBP61495
[31]
CommentsX-ray crystallography
PubMed ID11173468
JournalActa Crystallogr D Biol Crystallogr
Year2001
Volume57
Pages225-32
AuthorsQu C, Akanuma S, Tanaka N, Moriyama H, Oshima T
TitleDesign, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus.
Related PDB1g2u,1gc8,1gc9
[32]
PubMed ID11369782
JournalJ Biol Chem
Year2001
Volume276
Pages28121-5
AuthorsSvingor A, Kardos J, Hajdu I, Nemeth A, Zavodszky P
TitleA better enzyme to cope with cold. Comparative flexibility studies on psychrotrophic, mesophilic, and thermophilic IPMDHs.
[33]
PubMed ID11297665
JournalProtein Eng
Year2001
Volume14
Pages81-4
AuthorsHirose R, Suzuki T, Moriyama H, Sato T, Yamagishi A, Oshima T, Tanaka N
TitleCrystal structures of mutants of Thermus thermophilus IPMDH adapted to low temperatures.
[34]
PubMed ID11297666
JournalProtein Eng
Year2001
Volume14
Pages85-91
AuthorsSuzuki T, Yasugi M, Arisaka F, Yamagishi A, Oshima T
TitleAdaptation of a thermophilic enzyme, 3-isopropylmalate dehydrogenase, to low temperatures.

comments
This enzyme catalyzes two reactions; firstly the dehydrogenation of 3-carboxy-2-hydroxy-4-methylpentanoate, secondly decarboxylation of the dehydrogenated product.

createdupdated
2004-07-222009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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