LEU3_ECOLI
ID LEU3_ECOLI Reviewed; 363 AA.
AC P30125; P78043;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=3-isopropylmalate dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000303|PubMed:9003442};
DE EC=1.1.1.85 {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000269|PubMed:9003442};
DE AltName: Full=3-IPM-DH {ECO:0000255|HAMAP-Rule:MF_01033};
DE AltName: Full=Beta-IPM dehydrogenase {ECO:0000255|HAMAP-Rule:MF_01033};
DE Short=IMDH {ECO:0000255|HAMAP-Rule:MF_01033};
GN Name=leuB {ECO:0000255|HAMAP-Rule:MF_01033};
GN OrderedLocusNames=b0073, JW5807;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=8119295; DOI=10.1111/j.1432-1033.1994.tb18623.x;
RA Kirino H., Aoki M., Aoshima M., Hayashi Y., Ohba M., Yamagishi A.,
RA Wakagi T., Oshima T.;
RT "Hydrophobic interaction at the subunit interface contributes to the
RT thermostability of 3-isopropylmalate dehydrogenase from an extreme
RT thermophile, Thermus thermophilus.";
RL Eur. J. Biochem. 220:275-281(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12;
RX PubMed=1630901; DOI=10.1093/nar/20.13.3305;
RA Yura T., Mori H., Nagai H., Nagata T., Ishihama A., Fujita N., Isono K.,
RA Mizobuchi K., Nakata A.;
RT "Systematic sequencing of the Escherichia coli genome: analysis of the 0-
RT 2.4 min region.";
RL Nucleic Acids Res. 20:3305-3308(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP PROTEIN SEQUENCE OF 2-13.
RC STRAIN=K12 / EMG2;
RX PubMed=9298646; DOI=10.1002/elps.1150180807;
RA Link A.J., Robison K., Church G.M.;
RT "Comparing the predicted and observed properties of proteins encoded in the
RT genome of Escherichia coli K-12.";
RL Electrophoresis 18:1259-1313(1997).
RN [6]
RP PROTEIN SEQUENCE OF 2-11, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY
RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=9003442; DOI=10.1016/s0167-4838(96)00157-4;
RA Wallon G., Yamamoto K., Kirino H., Yamagishi A., Lovett S.T., Petsko G.A.,
RA Oshima T.;
RT "Purification, catalytic properties and thermostability of 3-
RT isopropylmalate dehydrogenase from Escherichia coli.";
RL Biochim. Biophys. Acta 1337:105-112(1997).
RN [7]
RP 3D-STRUCTURE MODELING.
RX PubMed=8875643; DOI=10.1093/protein/9.8.663;
RA Magyar C., Szilagyi A., Zavodszy P.;
RT "Relationship between thermal stability and 3-D structure in a homology
RT model of 3-isopropylmalate dehydrogenase from Escherichia coli.";
RL Protein Eng. 9:663-670(1996).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.06 ANGSTROMS), AND SUBUNIT.
RX PubMed=9086278; DOI=10.1006/jmbi.1996.0797;
RA Wallon G., Kryger G., Lovett S.T., Oshima T., Ringe D., Petsko G.A.;
RT "Crystal structures of Escherichia coli and Salmonella typhimurium 3-
RT isopropylmalate dehydrogenase and comparison with their thermophilic
RT counterpart from Thermus thermophilus.";
RL J. Mol. Biol. 266:1016-1031(1997).
CC -!- FUNCTION: Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-
CC methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-
CC oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate.
CC {ECO:0000255|HAMAP-Rule:MF_01033, ECO:0000269|PubMed:9003442}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate
CC + CO2 + NADH; Xref=Rhea:RHEA:32271, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17865, ChEBI:CHEBI:35121, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.85; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_01033, ECO:0000269|PubMed:9003442};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:9003442};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:9003442};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000255|HAMAP-
CC Rule:MF_01033};
CC -!- ACTIVITY REGULATION: Requires K(+) ions for optimum activity.
CC {ECO:0000269|PubMed:9003442}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=105 uM for 3-isopropylmalate (at 40 degrees Celsius)
CC {ECO:0000269|PubMed:9003442};
CC KM=321 uM for NAD (at 40 degrees Celsius)
CC {ECO:0000269|PubMed:9003442};
CC Note=kcat is 69 sec(-1). {ECO:0000269|PubMed:9003442};
CC pH dependence:
CC Optimum pH is 7.6. {ECO:0000269|PubMed:9003442};
CC Temperature dependence:
CC Optimum temperature is 70 degrees Celsius.
CC {ECO:0000269|PubMed:9003442};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4. {ECO:0000255|HAMAP-
CC Rule:MF_01033, ECO:0000305|PubMed:9003442}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01033,
CC ECO:0000269|PubMed:9086278}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01033}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. LeuB type 1 subfamily. {ECO:0000255|HAMAP-
CC Rule:MF_01033, ECO:0000305}.
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DR EMBL; D17631; BAA04537.1; -; Genomic_DNA.
DR EMBL; U00096; AAC73184.2; -; Genomic_DNA.
DR EMBL; AP009048; BAB96642.1; -; Genomic_DNA.
DR PIR; A64729; A64729.
DR RefSeq; NP_414615.4; NC_000913.3.
DR RefSeq; WP_000042353.1; NZ_STEB01000010.1.
DR PDB; 1CM7; X-ray; 2.06 A; A/B=1-363.
DR PDBsum; 1CM7; -.
DR AlphaFoldDB; P30125; -.
DR SMR; P30125; -.
DR BioGRID; 4259727; 8.
DR BioGRID; 849199; 2.
DR IntAct; P30125; 2.
DR STRING; 511145.b0073; -.
DR jPOST; P30125; -.
DR PaxDb; P30125; -.
DR PRIDE; P30125; -.
DR EnsemblBacteria; AAC73184; AAC73184; b0073.
DR EnsemblBacteria; BAB96642; BAB96642; BAB96642.
DR GeneID; 66671637; -.
DR GeneID; 944798; -.
DR KEGG; ecj:JW5807; -.
DR KEGG; eco:b0073; -.
DR PATRIC; fig|1411691.4.peg.2208; -.
DR EchoBASE; EB1537; -.
DR eggNOG; COG0473; Bacteria.
DR HOGENOM; CLU_031953_0_3_6; -.
DR InParanoid; P30125; -.
DR OMA; EYDLGAR; -.
DR PhylomeDB; P30125; -.
DR BioCyc; EcoCyc:3-ISOPROPYLMALDEHYDROG-MON; -.
DR BioCyc; MetaCyc:3-ISOPROPYLMALDEHYDROG-MON; -.
DR BRENDA; 1.1.1.85; 2026.
DR SABIO-RK; P30125; -.
DR UniPathway; UPA00048; UER00072.
DR EvolutionaryTrace; P30125; -.
DR PRO; PR:P30125; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IDA:EcoCyc.
DR GO; GO:0000287; F:magnesium ion binding; IDA:EcoCyc.
DR GO; GO:0030145; F:manganese ion binding; IDA:EcoCyc.
DR GO; GO:0046872; F:metal ion binding; IDA:EcoCyc.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IMP:EcoliWiki.
DR GO; GO:0009098; P:leucine biosynthetic process; IDA:EcoCyc.
DR HAMAP; MF_01033; LeuB_type1; 1.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR004429; Isopropylmalate_DH.
DR PANTHER; PTHR42979; PTHR42979; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00169; leuB; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Cytoplasm;
KW Direct protein sequencing; Leucine biosynthesis; Magnesium; Manganese;
KW Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:9003442,
FT ECO:0000269|PubMed:9298646"
FT CHAIN 2..363
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083691"
FT BINDING 78..91
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 99
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 109
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 138
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 227
FT /ligand="substrate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 251
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 255
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT BINDING 285..297
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT SITE 145
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT SITE 195
FT /note="Important for catalysis"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01033"
FT CONFLICT 2
FT /note="S -> D (in Ref. 6; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 3..13
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 16..34
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 37..42
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 47..53
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 59..66
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 68..75
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 86..89
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 90..101
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:1CM7"
FT TURN 118..120
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 121..123
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 125..128
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 143..145
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 148..153
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 160..168
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 169..184
FT /evidence="ECO:0007829|PDB:1CM7"
FT TURN 185..187
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:1CM7"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 200..212
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 219..225
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 226..235
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 237..239
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 241..245
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 247..261
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 278..284
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 299..311
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 316..331
FT /evidence="ECO:0007829|PDB:1CM7"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:1CM7"
FT HELIX 348..359
FT /evidence="ECO:0007829|PDB:1CM7"
SQ SEQUENCE 363 AA; 39517 MW; 125EC1034FE1A3B5 CRC64;
MSKNYHIAVL PGDGIGPEVM TQALKVLDAV RNRFAMRITT SHYDVGGAAI DNHGQPLPPA
TVEGCEQADA VLFGSVGGPK WEHLPPDQQP ERGALLPLRK HFKLFSNLRP AKLYQGLEAF
CPLRADIAAN GFDILCVREL TGGIYFGQPK GREGSGQYEK AFDTEVYHRF EIERIARIAF
ESARKRRHKV TSIDKANVLQ SSILWREIVN EIATEYPDVE LAHMYIDNAT MQLIKDPSQF
DVLLCSNLFG DILSDECAMI TGSMGMLPSA SLNEQGFGLY EPAGGSAPDI AGKNIANPIA
QILSLALLLR YSLDADDAAC AIERAINRAL EEGIRTGDLA RGAAAVSTDE MGDIIARYVA
EGV
