LEU3_THET8
ID LEU3_THET8 Reviewed; 345 AA.
AC Q5SIY4;
DT 24-MAY-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 125.
DE RecName: Full=3-isopropylmalate dehydrogenase;
DE EC=1.1.1.85;
DE AltName: Full=3-IPM-DH;
DE AltName: Full=Beta-IPM dehydrogenase;
DE Short=IMDH;
GN Name=leuB; OrderedLocusNames=TTHA1230;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Deinococcus-Thermus; Deinococci; Thermales; Thermaceae; Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=6321488; DOI=10.1016/s0021-9258(17)43242-x;
RA Kagawa Y., Nojima H., Nukiwa N., Ishizuka M., Nakajima T., Yasuhara T.,
RA Tanaka T., Oshima T.;
RT "High guanine plus cytosine content in the third letter of codons of an
RT extreme thermophile. DNA sequence of the isopropylmalate dehydrogenase of
RT Thermus thermophilus.";
RL J. Biol. Chem. 259:2956-2960(1984).
RN [2]
RP SEQUENCE REVISION.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP ENZYME KINETICS, AND MUTAGENESIS OF TYR-139.
RX PubMed=8405446; DOI=10.1016/0014-5793(93)80478-d;
RA Miyazaki K., Oshima T.;
RT "Tyr-139 in Thermus thermophilus 3-isopropylmalate dehydrogenase is
RT involved in catalytic function.";
RL FEBS Lett. 332:37-38(1993).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH NAD.
RX PubMed=7881901; DOI=10.1016/s0969-2126(94)00104-9;
RA Hurley J.H., Dean A.M.;
RT "Structure of 3-isopropylmalate dehydrogenase in complex with NAD+: ligand-
RT induced loop closing and mechanism for cofactor specificity.";
RL Structure 2:1007-1016(1994).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND SUBUNIT.
RX PubMed=15299625; DOI=10.1107/s0907444995016623;
RA Nagata C., Moriyama H., Tanaka N., Nakasako M., Yamamoto M., Ueki T.,
RA Oshima T.;
RT "Cryocrystallography of 3-Isopropylmalate dehydrogenase from Thermus
RT thermophilus and its chimeric enzyme.";
RL Acta Crystallogr. D 52:623-630(1996).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS), AND SUBUNIT.
RX PubMed=1748999; DOI=10.1016/0022-2836(91)90508-4;
RA Imada K., Sato M., Tanaka N., Katsube Y., Matsuura Y., Oshima T.;
RT "Three-dimensional structure of a highly thermostable enzyme, 3-
RT isopropylmalate dehydrogenase of Thermus thermophilus at 2.2-A
RT resolution.";
RL J. Mol. Biol. 222:725-738(1991).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10810156; DOI=10.1093/protein/13.4.253;
RA Nurachman Z., Akanuma S., Sato T., Oshima T., Tanaka N.;
RT "Crystal structures of 3-isopropylmalate dehydrogenase with mutations at
RT the C-terminus: crystallographic analyses of structure-stability
RT relationships.";
RL Protein Eng. 13:253-258(2000).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), AND SUBUNIT.
RX PubMed=11173468; DOI=10.1107/s0907444900017388;
RA Qu C., Akanuma S., Tanaka N., Moriyama H., Oshima T.;
RT "Design, X-ray crystallography, molecular modelling and thermal stability
RT studies of mutant enzymes at site 172 of 3-isopropylmalate dehydrogenase
RT from Thermus thermophilus.";
RL Acta Crystallogr. D 57:225-232(2001).
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 -!- 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;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.;
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1.26 uM for 3-isopropylmalate (at pH 8 and 60 degrees Celsius);
CC KM=40.9 uM for NAD;
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11173468,
CC ECO:0000269|PubMed:15299625, ECO:0000269|PubMed:1748999,
CC ECO:0000269|PubMed:7881901}.
CC -!- INTERACTION:
CC Q5SIY4; Q5SIY4: leuB; NbExp=2; IntAct=EBI-9699580, EBI-9699580;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. LeuB type 1 subfamily. {ECO:0000305}.
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DR EMBL; K01444; AAA16706.1; -; Genomic_DNA.
DR EMBL; AP008226; BAD71053.1; -; Genomic_DNA.
DR PIR; S41223; DETWIT.
DR RefSeq; WP_011228534.1; NC_006461.1.
DR RefSeq; YP_144496.1; NC_006461.1.
DR PDB; 1DPZ; X-ray; 2.80 A; A/B=1-345.
DR PDB; 1DR0; X-ray; 2.20 A; A/B=1-345.
DR PDB; 1DR8; X-ray; 2.70 A; A/B=1-344.
DR PDB; 1G2U; X-ray; 2.10 A; A=1-345.
DR PDB; 1GC8; X-ray; 2.50 A; A/B=1-345.
DR PDB; 1GC9; X-ray; 2.30 A; A=1-345.
DR PDB; 1HEX; X-ray; 2.50 A; A=1-345.
DR PDB; 1IDM; X-ray; 2.20 A; A=1-345.
DR PDB; 1IPD; X-ray; 2.20 A; A=1-345.
DR PDB; 1OSI; X-ray; 3.00 A; A/B/C/D=1-345.
DR PDB; 1OSJ; X-ray; 2.35 A; A/B=1-345.
DR PDB; 1XAA; X-ray; 2.10 A; A=1-345.
DR PDB; 1XAB; X-ray; 2.10 A; A=1-345.
DR PDB; 1XAC; X-ray; 2.10 A; A=1-345.
DR PDB; 1XAD; X-ray; 2.10 A; A=1-345.
DR PDB; 2Y3Z; X-ray; 1.83 A; A=1-345.
DR PDB; 2Y40; X-ray; 2.50 A; A/B=1-345.
DR PDB; 2Y41; X-ray; 2.20 A; A/B=1-345.
DR PDB; 2Y42; X-ray; 2.50 A; A/B/C/D=1-345.
DR PDB; 2ZTW; X-ray; 2.79 A; A=1-345.
DR PDB; 4F7I; X-ray; 2.00 A; A/B/C/D=1-345.
DR PDB; 4WUO; X-ray; 2.05 A; A/B=1-345.
DR PDBsum; 1DPZ; -.
DR PDBsum; 1DR0; -.
DR PDBsum; 1DR8; -.
DR PDBsum; 1G2U; -.
DR PDBsum; 1GC8; -.
DR PDBsum; 1GC9; -.
DR PDBsum; 1HEX; -.
DR PDBsum; 1IDM; -.
DR PDBsum; 1IPD; -.
DR PDBsum; 1OSI; -.
DR PDBsum; 1OSJ; -.
DR PDBsum; 1XAA; -.
DR PDBsum; 1XAB; -.
DR PDBsum; 1XAC; -.
DR PDBsum; 1XAD; -.
DR PDBsum; 2Y3Z; -.
DR PDBsum; 2Y40; -.
DR PDBsum; 2Y41; -.
DR PDBsum; 2Y42; -.
DR PDBsum; 2ZTW; -.
DR PDBsum; 4F7I; -.
DR PDBsum; 4WUO; -.
DR AlphaFoldDB; Q5SIY4; -.
DR PCDDB; Q5SIY4; -.
DR SMR; Q5SIY4; -.
DR MINT; Q5SIY4; -.
DR STRING; 300852.55772612; -.
DR BindingDB; Q5SIY4; -.
DR ChEMBL; CHEMBL3308964; -.
DR EnsemblBacteria; BAD71053; BAD71053; BAD71053.
DR GeneID; 3168996; -.
DR KEGG; ttj:TTHA1230; -.
DR PATRIC; fig|300852.9.peg.1209; -.
DR eggNOG; COG0473; Bacteria.
DR HOGENOM; CLU_031953_0_3_0; -.
DR OMA; EYDLGAR; -.
DR PhylomeDB; Q5SIY4; -.
DR BRENDA; 1.1.1.85; 2305.
DR SABIO-RK; Q5SIY4; -.
DR UniPathway; UPA00048; UER00072.
DR EvolutionaryTrace; Q5SIY4; -.
DR Proteomes; UP000000532; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
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; Leucine biosynthesis;
KW Magnesium; Manganese; Metal-binding; NAD; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..345
FT /note="3-isopropylmalate dehydrogenase"
FT /id="PRO_0000083775"
FT BINDING 74..87
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:7881901"
FT BINDING 94
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 104
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 132
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 241
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 245
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 274..286
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:7881901"
FT SITE 139
FT /note="Important for catalysis"
FT SITE 185
FT /note="Important for catalysis"
FT /evidence="ECO:0000250"
FT MUTAGEN 139
FT /note="Y->F: Large decrease in activity and a small
FT decrease in substrate affinity."
FT /evidence="ECO:0000269|PubMed:8405446"
FT CONFLICT 85
FT /note="R -> S (in Ref. 1; AAA16706)"
FT /evidence="ECO:0000305"
FT STRAND 1..6
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 12..30
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 34..38
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 43..49
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 50..53
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 55..63
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 64..69
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1IDM"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 86..96
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 113..115
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 120..123
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 135..137
FT /evidence="ECO:0007829|PDB:1GC9"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1XAC"
FT STRAND 148..158
FT /evidence="ECO:0007829|PDB:4F7I"
FT HELIX 159..174
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 178..184
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 190..203
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 209..215
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 216..225
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 231..235
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 237..248
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT TURN 249..251
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 254..256
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 258..265
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT STRAND 268..273
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:1XAD"
FT HELIX 288..300
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 305..321
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:2Y3Z"
FT HELIX 333..345
FT /evidence="ECO:0007829|PDB:2Y3Z"
SQ SEQUENCE 345 AA; 36780 MW; 3EFF8736312E2785 CRC64;
MKVAVLPGDG IGPEVTEAAL KVLRALDEAE GLGLAYEVFP FGGAAIDAFG EPFPEPTRKG
VEEAEAVLLG SVGGPKWDGL PRKIRPETGL LSLRKSQDLF ANLRPAKVFP GLERLSPLKE
EIARGVDVLI VRELTGGIYF GEPRGMSEAE AWNTERYSKP EVERVARVAF EAARKRRKHV
VSVDKANVLE VGEFWRKTVE EVGRGYPDVA LEHQYVDAMA MHLVRSPARF DVVVTGNIFG
DILSDLASVL PGSLGLLPSA SLGRGTPVFE PVHGSAPDIA GKGIANPTAA ILSAAMMLEH
AFGLVELARK VEDAVAKALL ETPPPDLGGS AGTEAFTATV LRHLA
