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Protein

3-isopropylmalate dehydrogenase

Gene

leuB

Organism
Escherichia coli (strain K12)
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.UniRule annotation1 Publication

Catalytic activityi

(2R,3S)-3-isopropylmalate + NAD+ = 4-methyl-2-oxopentanoate + CO2 + NADH.UniRule annotation1 Publication

Cofactori

Mg2+UniRule annotation1 Publication, Mn2+UniRule annotation1 PublicationNote: Binds 1 Mg2+ or Mn2+ ion per subunit.UniRule annotation

Enzyme regulationi

Requires K+ ions for optimum activity.1 Publication

Kineticsi

kcat is 69 sec(-1).1 Publication

  1. KM=105 µM for 3-isopropylmalate (at 40 degrees Celsius)1 Publication
  2. KM=321 µM for NAD (at 40 degrees Celsius)1 Publication

    pH dependencei

    Optimum pH is 7.6.1 Publication

    Temperature dependencei

    Optimum temperature is 70 degrees Celsius.1 Publication

    Pathwayi: L-leucine biosynthesis

    This protein is involved in step 3 of the subpathway that synthesizes L-leucine from 3-methyl-2-oxobutanoate.UniRule annotation1 Publication
    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 small subunit (leuD), 3-isopropylmalate dehydratase large subunit (leuC)
    3. 3-isopropylmalate dehydrogenase (leuB)
    4. Branched-chain-amino-acid aminotransferase (ilvE)
    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 sitei99 – 991SubstrateUniRule annotation
    Binding sitei109 – 1091SubstrateUniRule annotation
    Binding sitei138 – 1381SubstrateUniRule annotation
    Sitei145 – 1451Important for catalysisUniRule annotation
    Sitei195 – 1951Important for catalysisUniRule annotation
    Metal bindingi227 – 2271Magnesium or manganeseUniRule annotation
    Binding sitei227 – 2271SubstrateUniRule annotation
    Metal bindingi251 – 2511Magnesium or manganeseUniRule annotation
    Metal bindingi255 – 2551Magnesium or manganeseUniRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi78 – 9114NADUniRule annotationAdd
    BLAST
    Nucleotide bindingi285 – 29713NADUniRule annotationAdd
    BLAST

    GO - Molecular functioni

    • 3-isopropylmalate dehydrogenase activity Source: EcoCyc
    • magnesium ion binding Source: EcoCyc
    • manganese ion binding Source: EcoCyc
    • metal ion binding Source: EcoCyc
    • NAD binding Source: InterPro

    GO - Biological processi

    • cellular response to amino acid starvation Source: EcoliWiki
    • leucine biosynthetic process Source: EcoCyc
    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

    BioCyciEcoCyc:3-ISOPROPYLMALDEHYDROG-MONOMER.
    ECOL316407:JW5807-MONOMER.
    MetaCyc:3-ISOPROPYLMALDEHYDROG-MONOMER.
    BRENDAi1.1.1.85. 2026.
    UniPathwayiUPA00048; UER00072.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    3-isopropylmalate dehydrogenase1 PublicationUniRule annotation (EC:1.1.1.85UniRule annotation1 Publication)
    Alternative name(s):
    3-IPM-DHUniRule annotation
    Beta-IPM dehydrogenaseUniRule annotation
    Short name:
    IMDHUniRule annotation
    Gene namesi
    Name:leuBUniRule annotation
    Ordered Locus Names:b0073, JW5807
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG11577. leuB.

    Subcellular locationi

    • Cytoplasm UniRule annotation

    GO - Cellular componenti

    • cytosol Source: EcoCyc
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methionineiRemoved2 Publications
    Chaini2 – 3633623-isopropylmalate dehydrogenasePRO_0000083691Add
    BLAST

    Proteomic databases

    EPDiP30125.
    PaxDbiP30125.
    PRIDEiP30125.

    Interactioni

    Subunit structurei

    Homodimer.UniRule annotation1 Publication

    Protein-protein interaction databases

    BioGridi4259727. 8 interactions.
    IntActiP30125. 2 interactions.
    STRINGi511145.b0073.

    Structurei

    Secondary structure

    1
    363
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi3 – 1311Combined sources
    Helixi16 – 3419Combined sources
    Beta strandi37 – 426Combined sources
    Helixi47 – 537Combined sources
    Beta strandi54 – 574Combined sources
    Helixi59 – 668Combined sources
    Beta strandi68 – 758Combined sources
    Beta strandi86 – 894Combined sources
    Helixi90 – 10112Combined sources
    Beta strandi106 – 1127Combined sources
    Turni118 – 1203Combined sources
    Beta strandi121 – 1233Combined sources
    Helixi125 – 1284Combined sources
    Beta strandi133 – 1397Combined sources
    Helixi143 – 1453Combined sources
    Beta strandi148 – 1536Combined sources
    Helixi156 – 1583Combined sources
    Beta strandi160 – 1689Combined sources
    Helixi169 – 18416Combined sources
    Turni185 – 1873Combined sources
    Beta strandi188 – 1947Combined sources
    Turni196 – 1983Combined sources
    Helixi200 – 21213Combined sources
    Helixi213 – 2153Combined sources
    Beta strandi219 – 2257Combined sources
    Helixi226 – 23510Combined sources
    Helixi237 – 2393Combined sources
    Beta strandi241 – 2455Combined sources
    Helixi247 – 26115Combined sources
    Beta strandi268 – 2725Combined sources
    Beta strandi278 – 2847Combined sources
    Helixi288 – 2903Combined sources
    Helixi299 – 31113Combined sources
    Helixi316 – 33116Combined sources
    Beta strandi336 – 3383Combined sources
    Helixi348 – 35912Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CM7X-ray2.06A/B1-363[»]
    ProteinModelPortaliP30125.
    SMRiP30125. Positions 1-363.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP30125.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the isocitrate and isopropylmalate dehydrogenases family. LeuB type 1 subfamily.UniRule annotationCurated

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    HOGENOMiHOG000021112.
    InParanoidiP30125.
    KOiK00052.
    OMAiRRPKQFD.
    OrthoDBiEOG65N1BN.
    PhylomeDBiP30125.

    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.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P30125-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MSKNYHIAVL PGDGIGPEVM TQALKVLDAV RNRFAMRITT SHYDVGGAAI
    60 70 80 90 100
    DNHGQPLPPA TVEGCEQADA VLFGSVGGPK WEHLPPDQQP ERGALLPLRK
    110 120 130 140 150
    HFKLFSNLRP AKLYQGLEAF CPLRADIAAN GFDILCVREL TGGIYFGQPK
    160 170 180 190 200
    GREGSGQYEK AFDTEVYHRF EIERIARIAF ESARKRRHKV TSIDKANVLQ
    210 220 230 240 250
    SSILWREIVN EIATEYPDVE LAHMYIDNAT MQLIKDPSQF DVLLCSNLFG
    260 270 280 290 300
    DILSDECAMI TGSMGMLPSA SLNEQGFGLY EPAGGSAPDI AGKNIANPIA
    310 320 330 340 350
    QILSLALLLR YSLDADDAAC AIERAINRAL EEGIRTGDLA RGAAAVSTDE
    360
    MGDIIARYVA EGV
    Length:363
    Mass (Da):39,517
    Last modified:January 23, 2007 - v3
    Checksum:i125EC1034FE1A3B5
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti2 – 21S → D AA sequence (PubMed:9003442).Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D17631 Genomic DNA. Translation: BAA04537.1.
    U00096 Genomic DNA. Translation: AAC73184.2.
    AP009048 Genomic DNA. Translation: BAB96642.1.
    PIRiA64729.
    RefSeqiNP_414615.4. NC_000913.3.
    WP_000042353.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC73184; AAC73184; b0073.
    BAB96642; BAB96642; BAB96642.
    GeneIDi944798.
    KEGGiecj:JW5807.
    eco:b0073.
    PATRICi32115249. VBIEscCol129921_0076.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    D17631 Genomic DNA. Translation: BAA04537.1.
    U00096 Genomic DNA. Translation: AAC73184.2.
    AP009048 Genomic DNA. Translation: BAB96642.1.
    PIRiA64729.
    RefSeqiNP_414615.4. NC_000913.3.
    WP_000042353.1. NZ_LN832404.1.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1CM7X-ray2.06A/B1-363[»]
    ProteinModelPortaliP30125.
    SMRiP30125. Positions 1-363.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi4259727. 8 interactions.
    IntActiP30125. 2 interactions.
    STRINGi511145.b0073.

    Proteomic databases

    EPDiP30125.
    PaxDbiP30125.
    PRIDEiP30125.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC73184; AAC73184; b0073.
    BAB96642; BAB96642; BAB96642.
    GeneIDi944798.
    KEGGiecj:JW5807.
    eco:b0073.
    PATRICi32115249. VBIEscCol129921_0076.

    Organism-specific databases

    EchoBASEiEB1537.
    EcoGeneiEG11577. leuB.

    Phylogenomic databases

    eggNOGiENOG4105C0C. Bacteria.
    COG0473. LUCA.
    HOGENOMiHOG000021112.
    InParanoidiP30125.
    KOiK00052.
    OMAiRRPKQFD.
    OrthoDBiEOG65N1BN.
    PhylomeDBiP30125.

    Enzyme and pathway databases

    UniPathwayiUPA00048; UER00072.
    BioCyciEcoCyc:3-ISOPROPYLMALDEHYDROG-MONOMER.
    ECOL316407:JW5807-MONOMER.
    MetaCyc:3-ISOPROPYLMALDEHYDROG-MONOMER.
    BRENDAi1.1.1.85. 2026.

    Miscellaneous databases

    EvolutionaryTraceiP30125.
    PROiP30125.

    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. "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: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Strain: K12.
    2. "Systematic sequencing of the Escherichia coli genome: analysis of the 0-2.4 min region."
      Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K., Mizobuchi K., Nakata A.
      Nucleic Acids Res. 20:3305-3308(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    5. "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12."
      Link A.J., Robison K., Church G.M.
      Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-13.
      Strain: K12 / EMG2.
    6. "Purification, catalytic properties and thermostability of 3-isopropylmalate dehydrogenase from Escherichia coli."
      Wallon G., Yamamoto K., Kirino H., Yamagishi A., Lovett S.T., Petsko G.A., Oshima T.
      Biochim. Biophys. Acta 1337:105-112(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 2-11, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY.
    7. "Relationship between thermal stability and 3-D structure in a homology model of 3-isopropylmalate dehydrogenase from Escherichia coli."
      Magyar C., Szilagyi A., Zavodszy P.
      Protein Eng. 9:663-670(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: 3D-STRUCTURE MODELING.
    8. "Crystal structures of Escherichia coli and Salmonella typhimurium 3-isopropylmalate dehydrogenase and comparison with their thermophilic counterpart from Thermus thermophilus."
      Wallon G., Kryger G., Lovett S.T., Oshima T., Ringe D., Petsko G.A.
      J. Mol. Biol. 266:1016-1031(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS), SUBUNIT.

    Entry informationi

    Entry nameiLEU3_ECOLI
    AccessioniPrimary (citable) accession number: P30125
    Secondary accession number(s): P78043
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: January 23, 2007
    Last modified: May 11, 2016
    This is version 147 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. 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.