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Protein

3-isopropylmalate dehydrogenase

Gene

leuB

Organism
Thermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate.

Catalytic activityi

(2R,3S)-3-isopropylmalate + NAD+ = 4-methyl-2-oxopentanoate + CO2 + NADH.

Cofactori

Mg2+, Mn2+Note: Binds 1 Mg2+ or Mn2+ ion per subunit.

Kineticsi

  1. KM=1.26 µM for 3-isopropylmalate (at pH 8 and 60 degrees Celsius)
  2. KM=40.9 µM for NAD

    Pathwayi: L-leucine biosynthesis

    This protein is involved in step 3 of the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate.
    Proteins known to be involved in the 4 steps of the subpathway in this organism are:
    1. 2-isopropylmalate synthase (leuA)
    2. 3-isopropylmalate dehydratase large subunit (leuC), 3-isopropylmalate dehydratase small subunit (leuD), 3-isopropylmalate dehydratase large subunit (leuC)
    3. 3-isopropylmalate dehydrogenase (leuB)
    4. no protein annotated in this organism
    This subpathway is part of the pathway L-leucine biosynthesis, which is itself part of Amino-acid biosynthesis.
    View all proteins of this organism that are known to be involved in the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate, the pathway L-leucine biosynthesis and in Amino-acid biosynthesis.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei94 – 941SubstrateBy similarity
    Binding sitei104 – 1041SubstrateBy similarity
    Binding sitei132 – 1321SubstrateBy similarity
    Sitei139 – 1391Important for catalysis
    Sitei185 – 1851Important for catalysisBy similarity
    Metal bindingi217 – 2171Magnesium or manganeseBy similarity
    Binding sitei217 – 2171SubstrateBy similarity
    Metal bindingi241 – 2411Magnesium or manganeseBy similarity
    Metal bindingi245 – 2451Magnesium or manganeseBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi74 – 8714NAD1 PublicationAdd
    BLAST
    Nucleotide bindingi274 – 28613NAD1 PublicationAdd
    BLAST

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Oxidoreductase

    Keywords - Biological processi

    Amino-acid biosynthesis, Branched-chain amino acid biosynthesis, Leucine biosynthesis

    Keywords - Ligandi

    Magnesium, Manganese, Metal-binding, NAD

    Enzyme and pathway databases

    BioCyciTTHE300852:GH8R-1264-MONOMER.
    BRENDAi1.1.1.85. 2305.
    UniPathwayiUPA00048; UER00072.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3-isopropylmalate dehydrogenase (EC:1.1.1.85)
    Alternative name(s):
    3-IPM-DH
    Beta-IPM dehydrogenase
    Short name:
    IMDH
    Gene namesi
    Name:leuB
    Ordered Locus Names:TTHA1230
    OrganismiThermus thermophilus (strain HB8 / ATCC 27634 / DSM 579)
    Taxonomic identifieri300852 [NCBI]
    Taxonomic lineageiBacteriaDeinococcus-ThermusDeinococciThermalesThermaceaeThermus
    Proteomesi
    • UP000000532 Componenti: Chromosome

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi139 – 1391Y → F: Large decrease in activity and a small decrease in substrate affinity. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 3453453-isopropylmalate dehydrogenasePRO_0000083775Add
    BLAST

    Interactioni

    Subunit structurei

    Homodimer.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-9699580,EBI-9699580

    GO - Molecular functioni

    • identical protein binding Source: IntAct

    Protein-protein interaction databases

    STRINGi300852.TTHA1230.

    Structurei

    Secondary structure

    345
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi1 – 66Combined sources
    Helixi12 – 3019Combined sources
    Beta strandi34 – 385Combined sources
    Helixi43 – 497Combined sources
    Beta strandi50 – 534Combined sources
    Helixi55 – 639Combined sources
    Beta strandi64 – 696Combined sources
    Helixi75 – 773Combined sources
    Beta strandi78 – 803Combined sources
    Helixi82 – 843Combined sources
    Helixi86 – 9611Combined sources
    Beta strandi99 – 1079Combined sources
    Helixi113 – 1153Combined sources
    Beta strandi116 – 1183Combined sources
    Helixi120 – 1234Combined sources
    Beta strandi127 – 1337Combined sources
    Beta strandi135 – 1373Combined sources
    Turni138 – 1403Combined sources
    Beta strandi144 – 1463Combined sources
    Beta strandi148 – 15811Combined sources
    Helixi159 – 17416Combined sources
    Turni175 – 1773Combined sources
    Beta strandi178 – 1847Combined sources
    Turni186 – 1883Combined sources
    Helixi190 – 20314Combined sources
    Beta strandi209 – 2157Combined sources
    Helixi216 – 22510Combined sources
    Helixi227 – 2293Combined sources
    Beta strandi231 – 2355Combined sources
    Helixi237 – 24812Combined sources
    Turni249 – 2513Combined sources
    Helixi254 – 2563Combined sources
    Beta strandi258 – 2658Combined sources
    Beta strandi268 – 2736Combined sources
    Helixi277 – 2793Combined sources
    Turni280 – 2823Combined sources
    Helixi288 – 30013Combined sources
    Helixi305 – 32117Combined sources
    Helixi325 – 3273Combined sources
    Helixi333 – 34513Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DPZX-ray2.80A/B1-345[»]
    1DR0X-ray2.20A/B1-345[»]
    1DR8X-ray2.70A/B1-344[»]
    1G2UX-ray2.10A1-345[»]
    1GC8X-ray2.50A/B1-345[»]
    1GC9X-ray2.30A1-345[»]
    1HEXX-ray2.50A1-345[»]
    1IDMX-ray2.20A1-345[»]
    1IPDX-ray2.20A1-345[»]
    1OSIX-ray3.00A/B/C/D1-345[»]
    1OSJX-ray2.35A/B1-345[»]
    1XAAX-ray2.10A1-345[»]
    1XABX-ray2.10A1-345[»]
    1XACX-ray2.10A1-345[»]
    1XADX-ray2.10A1-345[»]
    2Y3ZX-ray1.83A1-345[»]
    2Y40X-ray2.50A/B1-345[»]
    2Y41X-ray2.20A/B1-345[»]
    2Y42X-ray2.50A/B/C/D1-345[»]
    2ZTWX-ray2.79A1-345[»]
    4F7IX-ray2.00A/B/C/D1-345[»]
    4WUOX-ray2.05A/B1-345[»]
    ProteinModelPortaliQ5SIY4.
    SMRiQ5SIY4. Positions 1-345.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ5SIY4.

    Family & Domainsi

    Sequence similaritiesi

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    HOGENOMiHOG000021112.
    KOiK00052.
    OMAiHCGPEVV.
    OrthoDBiEOG65N1BN.
    PhylomeDBiQ5SIY4.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    HAMAPiMF_01033. LeuB_type1.
    InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
    IPR001804. Isocitrate/isopropylmalate_DH.
    IPR024084. IsoPropMal-DH-like_dom.
    IPR004429. Isopropylmalate_DH.
    [Graphical view]
    PANTHERiPTHR11835. PTHR11835. 1 hit.
    PfamiPF00180. Iso_dh. 1 hit.
    [Graphical view]
    SMARTiSM01329. Iso_dh. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00169. leuB. 1 hit.
    PROSITEiPS00470. IDH_IMDH. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q5SIY4-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MKVAVLPGDG IGPEVTEAAL KVLRALDEAE GLGLAYEVFP FGGAAIDAFG
    60 70 80 90 100
    EPFPEPTRKG VEEAEAVLLG SVGGPKWDGL PRKIRPETGL LSLRKSQDLF
    110 120 130 140 150
    ANLRPAKVFP GLERLSPLKE EIARGVDVLI VRELTGGIYF GEPRGMSEAE
    160 170 180 190 200
    AWNTERYSKP EVERVARVAF EAARKRRKHV VSVDKANVLE VGEFWRKTVE
    210 220 230 240 250
    EVGRGYPDVA LEHQYVDAMA MHLVRSPARF DVVVTGNIFG DILSDLASVL
    260 270 280 290 300
    PGSLGLLPSA SLGRGTPVFE PVHGSAPDIA GKGIANPTAA ILSAAMMLEH
    310 320 330 340
    AFGLVELARK VEDAVAKALL ETPPPDLGGS AGTEAFTATV LRHLA
    Length:345
    Mass (Da):36,780
    Last modified:December 21, 2004 - v1
    Checksum:i3EFF8736312E2785
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti85 – 851R → S in AAA16706 (PubMed:6321488).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    K01444 Genomic DNA. Translation: AAA16706.1.
    AP008226 Genomic DNA. Translation: BAD71053.1.
    PIRiS41223. DETWIT.
    RefSeqiWP_011228534.1. NC_006461.1.
    YP_144496.1. NC_006461.1.

    Genome annotation databases

    EnsemblBacteriaiBAD71053; BAD71053; BAD71053.
    GeneIDi3168996.
    KEGGittj:TTHA1230.
    PATRICi23957423. VBITheThe93045_1209.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    K01444 Genomic DNA. Translation: AAA16706.1.
    AP008226 Genomic DNA. Translation: BAD71053.1.
    PIRiS41223. DETWIT.
    RefSeqiWP_011228534.1. NC_006461.1.
    YP_144496.1. NC_006461.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1DPZX-ray2.80A/B1-345[»]
    1DR0X-ray2.20A/B1-345[»]
    1DR8X-ray2.70A/B1-344[»]
    1G2UX-ray2.10A1-345[»]
    1GC8X-ray2.50A/B1-345[»]
    1GC9X-ray2.30A1-345[»]
    1HEXX-ray2.50A1-345[»]
    1IDMX-ray2.20A1-345[»]
    1IPDX-ray2.20A1-345[»]
    1OSIX-ray3.00A/B/C/D1-345[»]
    1OSJX-ray2.35A/B1-345[»]
    1XAAX-ray2.10A1-345[»]
    1XABX-ray2.10A1-345[»]
    1XACX-ray2.10A1-345[»]
    1XADX-ray2.10A1-345[»]
    2Y3ZX-ray1.83A1-345[»]
    2Y40X-ray2.50A/B1-345[»]
    2Y41X-ray2.20A/B1-345[»]
    2Y42X-ray2.50A/B/C/D1-345[»]
    2ZTWX-ray2.79A1-345[»]
    4F7IX-ray2.00A/B/C/D1-345[»]
    4WUOX-ray2.05A/B1-345[»]
    ProteinModelPortaliQ5SIY4.
    SMRiQ5SIY4. Positions 1-345.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi300852.TTHA1230.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiBAD71053; BAD71053; BAD71053.
    GeneIDi3168996.
    KEGGittj:TTHA1230.
    PATRICi23957423. VBITheThe93045_1209.

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    HOGENOMiHOG000021112.
    KOiK00052.
    OMAiHCGPEVV.
    OrthoDBiEOG65N1BN.
    PhylomeDBiQ5SIY4.

    Enzyme and pathway databases

    UniPathwayiUPA00048; UER00072.
    BioCyciTTHE300852:GH8R-1264-MONOMER.
    BRENDAi1.1.1.85. 2305.

    Miscellaneous databases

    EvolutionaryTraceiQ5SIY4.

    Family and domain databases

    Gene3Di3.40.718.10. 1 hit.
    HAMAPiMF_01033. LeuB_type1.
    InterProiIPR019818. IsoCit/isopropylmalate_DH_CS.
    IPR001804. Isocitrate/isopropylmalate_DH.
    IPR024084. IsoPropMal-DH-like_dom.
    IPR004429. Isopropylmalate_DH.
    [Graphical view]
    PANTHERiPTHR11835. PTHR11835. 1 hit.
    PfamiPF00180. Iso_dh. 1 hit.
    [Graphical view]
    SMARTiSM01329. Iso_dh. 1 hit.
    [Graphical view]
    TIGRFAMsiTIGR00169. leuB. 1 hit.
    PROSITEiPS00470. IDH_IMDH. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "High guanine plus cytosine content in the third letter of codons of an extreme thermophile. DNA sequence of the isopropylmalate dehydrogenase of Thermus thermophilus."
      Kagawa Y., Nojima H., Nukiwa N., Ishizuka M., Nakajima T., Yasuhara T., Tanaka T., Oshima T.
      J. Biol. Chem. 259:2956-2960(1984) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Hydrophobic interaction at the subunit interface contributes to the thermostability of 3-isopropylmalate dehydrogenase from an extreme thermophile, Thermus thermophilus."
      Kirino H., Aoki M., Aoshima M., Hayashi Y., Ohba M., Yamagishi A., Wakagi T., Oshima T.
      Eur. J. Biochem. 220:275-281(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: SEQUENCE REVISION.
    3. "Complete genome sequence of Thermus thermophilus HB8."
      Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T., Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.
      Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: HB8 / ATCC 27634 / DSM 579.
    4. "Tyr-139 in Thermus thermophilus 3-isopropylmalate dehydrogenase is involved in catalytic function."
      Miyazaki K., Oshima T.
      FEBS Lett. 332:37-38(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: ENZYME KINETICS, MUTAGENESIS OF TYR-139.
    5. "Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-induced loop closing and mechanism for cofactor specificity."
      Hurley J.H., Dean A.M.
      Structure 2:1007-1016(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD.
    6. "Cryocrystallography of 3-Isopropylmalate dehydrogenase from Thermus thermophilus and its chimeric enzyme."
      Nagata C., Moriyama H., Tanaka N., Nakasako M., Yamamoto M., Ueki T., Oshima T.
      Acta Crystallogr. D 52:623-630(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBUNIT.
    7. "Three-dimensional structure of a highly thermostable enzyme, 3-isopropylmalate dehydrogenase of Thermus thermophilus at 2.2-A resolution."
      Imada K., Sato M., Tanaka N., Katsube Y., Matsuura Y., Oshima T.
      J. Mol. Biol. 222:725-738(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), SUBUNIT.
    8. "Crystal structures of 3-isopropylmalate dehydrogenase with mutations at the C-terminus: crystallographic analyses of structure-stability relationships."
      Nurachman Z., Akanuma S., Sato T., Oshima T., Tanaka N.
      Protein Eng. 13:253-258(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
    9. "Design, X-ray crystallography, molecular modelling and thermal stability studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase from Thermus thermophilus."
      Qu C., Akanuma S., Tanaka N., Moriyama H., Oshima T.
      Acta Crystallogr. D 57:225-232(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), SUBUNIT.

    Entry informationi

    Entry nameiLEU3_THET8
    AccessioniPrimary (citable) accession number: Q5SIY4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 24, 2005
    Last sequence update: December 21, 2004
    Last modified: May 11, 2016
    This is version 96 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.