LEU3_METJA
ID LEU3_METJA Reviewed; 333 AA.
AC Q58130;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-DEC-1998, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=3-isopropylmalate/3-methylmalate dehydrogenase;
DE EC=1.1.1.85;
DE EC=1.1.1.n5;
DE AltName: Full=3-isopropylmalate dehydrogenase;
DE Short=3-IPM-DH;
DE Short=IMDH;
DE Short=IPMDH;
DE AltName: Full=Beta-IPM dehydrogenase;
DE AltName: Full=D-malate dehydrogenase [decarboxylating];
DE EC=1.1.1.83;
GN Name=leuB; OrderedLocusNames=MJ0720;
OS Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS 10045 / NBRC 100440) (Methanococcus jannaschii).
OC Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC Methanocaldococcaceae; Methanocaldococcus.
OX NCBI_TaxID=243232;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT jannaschii.";
RL Science 273:1058-1073(1996).
RN [2]
RP CHARACTERIZATION.
RX PubMed=10940051; DOI=10.1128/jb.182.17.5013-5016.2000;
RA Howell D.M., Graupner M., Xu H., White R.H.;
RT "Identification of enzymes homologous to isocitrate dehydrogenase that are
RT involved in coenzyme B and leucine biosynthesis in methanoarchaea.";
RL J. Bacteriol. 182:5013-5016(2000).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, KINETIC PARAMETERS,
RP AND SUBUNIT.
RC STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX PubMed=17449626; DOI=10.1128/jb.00166-07;
RA Drevland R.M., Waheed A., Graham D.E.;
RT "Enzymology and evolution of the pyruvate pathway to 2-oxobutyrate in
RT Methanocaldococcus jannaschii.";
RL J. Bacteriol. 189:4391-4400(2007).
CC -!- FUNCTION: Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-
CC methylpentanoate (3-isopropylmalate) to 3-carboxy-4-methyl-2-
CC oxopentanoate, which decarboxylates to 4-methyl-2-oxopentanoate (2-
CC oxoisocaproate). Also catalyzes the oxidative decarboxylation of 3-
CC methylmalate to 2-oxobutyrate, and that of D-malate to pyruvate. Cannot
CC use NADP(+) instead of NAD(+). Cannot catalyze the oxidation of L-
CC malate, L-tartrate, D-tartrate, DL-isocitrate, or DL-lactate.
CC {ECO:0000269|PubMed:17449626}.
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 Evidence={ECO:0000269|PubMed:17449626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-methylmalate + NAD(+) = 2-oxobutanoate + CO2 + NADH;
CC Xref=Rhea:RHEA:32715, ChEBI:CHEBI:16526, ChEBI:CHEBI:16763,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945, ChEBI:CHEBI:58511; EC=1.1.1.n5;
CC Evidence={ECO:0000269|PubMed:17449626};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-malate + NAD(+) = CO2 + NADH + pyruvate;
CC Xref=Rhea:RHEA:18365, ChEBI:CHEBI:15361, ChEBI:CHEBI:15588,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.83;
CC Evidence={ECO:0000269|PubMed:17449626};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=24 uM for 3-isopropylmalate {ECO:0000269|PubMed:17449626};
CC KM=410 uM for D-malate {ECO:0000269|PubMed:17449626};
CC Temperature dependence:
CC Loses 50% of its activity after heating at 80 degrees Celsius for 10
CC min.;
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4.
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; 2-
CC oxobutanoate from pyruvate: step 3/3.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:17449626}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
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DR EMBL; L77117; AAB98716.1; -; Genomic_DNA.
DR RefSeq; WP_010870225.1; NC_000909.1.
DR AlphaFoldDB; Q58130; -.
DR SMR; Q58130; -.
DR STRING; 243232.MJ_0720; -.
DR EnsemblBacteria; AAB98716; AAB98716; MJ_0720.
DR GeneID; 1451597; -.
DR KEGG; mja:MJ_0720; -.
DR eggNOG; arCOG01163; Archaea.
DR HOGENOM; CLU_031953_0_1_2; -.
DR InParanoid; Q58130; -.
DR OMA; TCAHKAN; -.
DR OrthoDB; 33452at2157; -.
DR PhylomeDB; Q58130; -.
DR BioCyc; MetaCyc:MON-13649; -.
DR SABIO-RK; Q58130; -.
DR UniPathway; UPA00047; UER00069.
DR UniPathway; UPA00048; UER00072.
DR Proteomes; UP000000805; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0046553; F:D-malate dehydrogenase (decarboxylating) activity; IEA:UniProtKB-EC.
DR GO; GO:0004449; F:isocitrate dehydrogenase (NAD+) activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0019298; P:coenzyme B biosynthetic process; IDA:MENGO.
DR GO; GO:0006102; P:isocitrate metabolic process; IBA:GO_Central.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR011828; LEU3_arc.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR02088; LEU3_arch; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Cytoplasm;
KW Isoleucine biosynthesis; Leucine biosynthesis; Magnesium; Manganese;
KW Metal-binding; NAD; Oxidoreductase; Reference proteome.
FT CHAIN 1..333
FT /note="3-isopropylmalate/3-methylmalate dehydrogenase"
FT /id="PRO_0000083809"
FT BINDING 81
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 91
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 203
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 227
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 231
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 260..272
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250"
FT SITE 119
FT /note="Important for catalysis"
FT /evidence="ECO:0000250"
FT SITE 170
FT /note="Important for catalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 333 AA; 36330 MW; 0618F119A4E682F0 CRC64;
MHKICVIEGD GIGKEVVPAT IQVLEATGLP FEFVYAEAGD EVYKRTGKAL PEETIETALD
CDAVLFGAAG ETAADVIVKL RHILDTYANI RPVKAYKGVK CLRPDIDYVI VRENTEGLYK
GIEAEIDEGI TIATRVITEK ACERIFRFAF NLARERKKMG KEGKVTCAHK ANVLKLTDGL
FKKIFYKVAE EYDDIKAEDY YIDAMNMYII TKPQVFDVVV TSNLFGDILS DGAAGTVGGL
GLAPSANIGD EHGLFEPVHG SAPDIAGKKI ANPTATILSA VLMLRYLGEY EAADKVEKAL
EEVLALGLTT PDLGGNLNTF EMAEEVAKRV REE
