ID   LEU3_KLUMA              Reviewed;         359 AA.
AC   P41766;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 93.
DE   RecName: Full=3-isopropylmalate dehydrogenase;
DE            Short=3-IPM-DH;
DE            Short=IMDH;
DE            EC=1.1.1.85;
DE   AltName: Full=Beta-IPM dehydrogenase;
GN   Name=LEU2;
OS   Kluyveromyces marxianus (Yeast) (Candida kefyr).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Kluyveromyces.
OX   NCBI_TaxID=4911;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 26548 / CBS 6556 / NRRL Y-7571;
RX   PubMed=1803820; DOI=10.1002/yea.320070908;
RA   Bergkamp R.J.M., Geerse R.H., Verbakel J.M.A., Musters W., Planta R.J.;
RT   "Cloning and disruption of the LEU2 gene of Kluyveromyces marxianus CBS
RT   6556.";
RL   Yeast 7:963-970(1991).
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; 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   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 3/4.
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC       dehydrogenases family. {ECO:0000305}.
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DR   EMBL; X61490; CAA43710.1; -; Genomic_DNA.
DR   PIR; S32969; S32969.
DR   AlphaFoldDB; P41766; -.
DR   SMR; P41766; -.
DR   UniPathway; UPA00048; UER00072.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IEA:UniProtKB-EC.
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-UniPathway.
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   3: Inferred from homology;
KW   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; Cytoplasm;
KW   Leucine biosynthesis; Magnesium; Manganese; Metal-binding; NAD;
KW   Oxidoreductase.
FT   CHAIN           1..359
FT                   /note="3-isopropylmalate dehydrogenase"
FT                   /id="PRO_0000083611"
FT   BINDING         74..85
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         92
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         102
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         131
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         220
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         220
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         245
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         249
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         284..295
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            138
FT                   /note="Important for catalysis"
FT                   /evidence="ECO:0000250"
FT   SITE            187
FT                   /note="Important for catalysis"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   359 AA;  38315 MW;  E83119D85AB595AE CRC64;
     MSKNIVVLPG DHVGTEITNE AIKVLNAISE ARPSIKFNFE HHLIGGAAID ATGVPLPDEA
     SKKADAVLLG AVGGPKWGTG SVRPEQGLLK IRKELGLYAN LRPCNFASDS LLDLSPLKPE
     YAKGTDFVVV RELVGGIYFG ERKEDEGDGV AWDSEKYSVP EVQRITRMAA FLALQHNPPL
     PIWSLDKANV LASSRLWRKT VEETIKNEFP QLTVQHQLID SAAMILVKSP TKLNGIVITN
     NMFGDIISDE ASVIPGSLGL LPSASLASLP DTNKAFGLYE PCHGSAPDLP ANKVNPIATI
     LSAAMMLKLS LDLVEEGRAV EEAVRKVLDS GIRTGDLGGS NSTTEVGDAV AKAVKEILA