ID   LEU3_CANBO              Reviewed;         365 AA.
AC   Q01987;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-APR-1993, sequence version 1.
DT   03-AUG-2022, entry version 99.
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   Candida boidinii (Yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Pichiaceae; Ogataea; Ogataea/Candida clade.
OX   NCBI_TaxID=5477;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1522074; DOI=10.1128/jb.174.18.5988-5993.1992;
RA   Sakai Y., Tani Y.;
RT   "Directed mutagenesis in an asporogenous methylotrophic yeast: cloning,
RT   sequencing, and one-step gene disruption of the 3-isopropylmalate
RT   dehydrogenase gene (LEU2) of Candida boidinii to derive doubly auxotrophic
RT   marker strains.";
RL   J. Bacteriol. 174:5988-5993(1992).
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; M98832; AAA34349.1; -; Genomic_DNA.
DR   PIR; A43324; A43324.
DR   AlphaFoldDB; Q01987; -.
DR   SMR; Q01987; -.
DR   OrthoDB; 868374at2759; -.
DR   BRENDA; 1.1.1.85; 1100.
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..365
FT                   /note="3-isopropylmalate dehydrogenase"
FT                   /id="PRO_0000083602"
FT   BINDING         80..91
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         98
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         108
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         137
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         226
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         226
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         251
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         255
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000250"
FT   BINDING         290..301
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   SITE            144
FT                   /note="Important for catalysis"
FT                   /evidence="ECO:0000250"
FT   SITE            193
FT                   /note="Important for catalysis"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   365 AA;  39124 MW;  D3B0B89858653BCF CRC64;
     MSIIEKKIVL LPGDHVGVEV VEEAVKILKS ISEVKPEIQF KFENHLIGGA AIDATGVPLP
     DEALEAAKKS DAVLLGAVGG PKWGTGEVRP EQGLLKIRKE LNLYANLRPC NFASDKLLDL
     SPLKSDIVKG TDFTVVRELV GGIYFGDRVE DDGSGFASDS ESYSVPEVER ITRMAAFLSL
     QNDPPLPIWS LDKANVLASS RLWRKTVDRV IKEEFPKLTV QHQLIDSAAM ILVKSPTKLN
     GIVITNNMFG DIISDEASVI PGSLGLLPSA SLASLPDTNQ AFGLYEPCHG SAPDLPKNKV
     NPIATILSAA MMLKLSLNLV KEGNAVEEAV RKVLDQGIMT GDLGGNNSTT EVGDAIAKEV
     KLLLA