ID   LEU1_AQUAE              Reviewed;         520 AA.
AC   O67862;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   26-JUL-2002, sequence version 2.
DT   25-MAY-2022, entry version 128.
DE   RecName: Full=2-isopropylmalate synthase;
DE            EC=2.3.3.13;
DE   AltName: Full=Alpha-IPM synthase;
DE   AltName: Full=Alpha-isopropylmalate synthase;
GN   Name=leuA; OrderedLocusNames=aq_2090;
OS   Aquifex aeolicus (strain VF5).
OC   Bacteria; Aquificae; Aquificales; Aquificaceae; Aquifex.
OX   NCBI_TaxID=224324;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=VF5;
RX   PubMed=9537320; DOI=10.1038/32831;
RA   Deckert G., Warren P.V., Gaasterland T., Young W.G., Lenox A.L.,
RA   Graham D.E., Overbeek R., Snead M.A., Keller M., Aujay M., Huber R.,
RA   Feldman R.A., Short J.M., Olsen G.J., Swanson R.V.;
RT   "The complete genome of the hyperthermophilic bacterium Aquifex aeolicus.";
RL   Nature 392:353-358(1998).
CC   -!- FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA
CC       with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-
CC       hydroxy-4-methylpentanoate (2-isopropylmalate). {ECO:0000250}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=3-methyl-2-oxobutanoate + acetyl-CoA + H2O = (2S)-2-
CC         isopropylmalate + CoA + H(+); Xref=Rhea:RHEA:21524, ChEBI:CHEBI:1178,
CC         ChEBI:CHEBI:11851, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57287, ChEBI:CHEBI:57288; EC=2.3.3.13;
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 1 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAC07824.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AE000657; AAC07824.1; ALT_INIT; Genomic_DNA.
DR   PIR; B70479; B70479.
DR   RefSeq; NP_214431.1; NC_000918.1.
DR   AlphaFoldDB; O67862; -.
DR   SMR; O67862; -.
DR   STRING; 224324.aq_2090; -.
DR   EnsemblBacteria; AAC07824; AAC07824; aq_2090.
DR   KEGG; aae:aq_2090; -.
DR   PATRIC; fig|224324.8.peg.1611; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_022158_0_1_0; -.
DR   InParanoid; O67862; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 840579at2; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000798; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IBA:GO_Central.
DR   GO; GO:0009098; P:leucine biosynthetic process; IBA:GO_Central.
DR   Gene3D; 3.20.20.70; -; 1.
DR   Gene3D; 3.30.160.270; -; 1.
DR   HAMAP; MF_01025; LeuA_type1; 1.
DR   InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR   InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR   InterPro; IPR005671; LeuA_bact_synth.
DR   InterPro; IPR000891; PYR_CT.
DR   Pfam; PF00682; HMGL-like; 1.
DR   Pfam; PF08502; LeuA_dimer; 1.
DR   SMART; SM00917; LeuA_dimer; 1.
DR   SUPFAM; SSF110921; SSF110921; 1.
DR   TIGRFAMs; TIGR00973; leuA_bact; 1.
DR   PROSITE; PS00815; AIPM_HOMOCIT_SYNTH_1; 1.
DR   PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR   PROSITE; PS50991; PYR_CT; 1.
PE   3: Inferred from homology;
KW   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW   Leucine biosynthesis; Reference proteome; Transferase.
FT   CHAIN           1..520
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140328"
FT   DOMAIN          5..268
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   520 AA;  58103 MW;  95B210FA872871D4 CRC64;
     MGEKVYIFDT TLRDGEQAPG FSMTTEEKLQ MAHQLAKLNV DIIEAGFAAA SKGDFEAVNR
     IAKEVKGPVI CSLARALESD IEIAAKALEP AERKRIHTFI ATSPIHMEYK LRMTPDQVLE
     RIKKAVSFAR NFTDDVEFSC EDATRSEREF LYRAIETAIK HGATVINIPD TVGYAIPEEF
     GQLIEDIMNN VPNIDKVILS VHCHDDLGLA TANSLTAVKH GARQVECTIN GIGERAGNAA
     LEEVVMALKV RKDFFGDLYT DVNTKEIYKT SRLLCRITGN FVQPNKAIVG DNAFAHESGI
     HQHGVLSHRM TYEIMNPEDV GFPMSRIVLG KHSGRHALKR RLEELGFKFT KEELDRIFEK
     FKELADRKKE VYDEDLEALI YQEFMKIEDH EPVKVLHFQV QSGDNMIPTA TVKLEFKGEE
     REASSTGNGP VDATIKAIQK ALGIEPKLLD YSIKALTPNT DAQAEARVVL ELDGVKASGR
     GVDTDIIKAS VKAFTDALNR AIVRKEYIIQ RQEIREEGTV