ID   LEU1_MYCBO              Reviewed;         701 AA.
AC   Q7TVV6; A0A1R3Y5D6; X2BP46;
DT   15-DEC-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2003, sequence version 1.
DT   25-MAY-2022, entry version 108.
DE   RecName: Full=2-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_00572};
DE            EC=2.3.3.13 {ECO:0000255|HAMAP-Rule:MF_00572};
DE   AltName: Full=Alpha-IPM synthase {ECO:0000255|HAMAP-Rule:MF_00572};
DE   AltName: Full=Alpha-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_00572};
GN   Name=leuA {ECO:0000255|HAMAP-Rule:MF_00572};
GN   OrderedLocusNames=BQ2027_MB3737;
OS   Mycobacterium bovis (strain ATCC BAA-935 / AF2122/97).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=233413;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC BAA-935 / AF2122/97;
RX   PubMed=12788972; DOI=10.1073/pnas.1130426100;
RA   Garnier T., Eiglmeier K., Camus J.-C., Medina N., Mansoor H., Pryor M.,
RA   Duthoy S., Grondin S., Lacroix C., Monsempe C., Simon S., Harris B.,
RA   Atkin R., Doggett J., Mayes R., Keating L., Wheeler P.R., Parkhill J.,
RA   Barrell B.G., Cole S.T., Gordon S.V., Hewinson R.G.;
RT   "The complete genome sequence of Mycobacterium bovis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:7877-7882(2003).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC   STRAIN=ATCC BAA-935 / AF2122/97;
RX   PubMed=28385856; DOI=10.1128/genomea.00157-17;
RA   Malone K.M., Farrell D., Stuber T.P., Schubert O.T., Aebersold R.,
RA   Robbe-Austerman S., Gordon S.V.;
RT   "Updated reference genome sequence and annotation of Mycobacterium bovis
RT   AF2122/97.";
RL   Genome Announc. 5:E00157-E00157(2017).
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:0000255|HAMAP-
CC       Rule:MF_00572}.
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         Evidence={ECO:0000255|HAMAP-Rule:MF_00572};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000255|HAMAP-
CC       Rule:MF_00572}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00572}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 2 subfamily. {ECO:0000255|HAMAP-Rule:MF_00572}.
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DR   EMBL; LT708304; SIU02366.1; -; Genomic_DNA.
DR   RefSeq; WP_023349635.1; NC_002945.4.
DR   AlphaFoldDB; Q7TVV6; -.
DR   SMR; Q7TVV6; -.
DR   EnsemblBacteria; SIU02366; SIU02366; BQ2027_MB3737.
DR   OMA; WPDKVID; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001419; Chromosome.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IEA:UniProtKB-UniRule.
DR   GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR   CDD; cd07942; DRE_TIM_LeuA; 1.
DR   Gene3D; 3.20.20.70; -; 1.
DR   Gene3D; 3.30.160.270; -; 2.
DR   HAMAP; MF_00572; LeuA_type2; 1.
DR   InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR   InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR005668; IPM_Synthase.
DR   InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR   InterPro; IPR039371; LeuA_N_DRE-TIM.
DR   InterPro; IPR000891; PYR_CT.
DR   Pfam; PF00682; HMGL-like; 1.
DR   Pfam; PF08502; LeuA_dimer; 2.
DR   SMART; SM00917; LeuA_dimer; 1.
DR   SUPFAM; SSF110921; SSF110921; 2.
DR   TIGRFAMs; TIGR00970; leuA_yeast; 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; Transferase.
FT   CHAIN           1..701
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140434"
FT   DOMAIN          72..346
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT   REGION          1..40
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          577..671
FT                   /note="Insert"
FT   REGION          581..670
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   701 AA;  75683 MW;  1B0B3AC9C3A1533C CRC64;
     MTTSESPDAY TESFGAHTIV KPAGPPRVGQ PSWNPQRASS MPVNRYRPFA EEVEPIRLRN
     RTWPDRVIDR APLWCAVDLR DGNQALIDPM SPARKRRMFD LLVRMGYKEI EVGFPSASQT
     DFDFVREIIE QGAIPDDVTI QVLTQCRPEL IERTFQACSG AHRAIVHFYN STSILQRRVV
     FRANRAEVQA IATDGARKCV EQAAKYPGTQ WRFEYSPESY TGTELEYAKQ VCDAVGEVIA
     PTPERPIIFN LPATVEMTTP NVYADSIEWM SRNLANRESV ILSLHPHNDR GTAVAAAELG
     FAAGADRIEG CLFGNGERTG NVCLVTLGLN LFSRGVDPQI DFSNIDEIRR TVEYCNQLPV
     HERHPYGGDL VYTAFSGSHQ DAINKGLDAM KLDADAADCD VDDMLWQVPY LPIDPRDVGR
     TYEAVIRVNS QSGKGGVAYI MKTDHGLSLP RRLQIEFSQV IQKIAEGTAG EGGEVSPKEM
     WDAFAEEYLA PVRPLERIRQ HVDAADDDGG TTSITATVKI NGVETEISGS GNGPLAAFVH
     ALADVGFDVA VLDYYEHAMS AGDDAQAAAY VEASVTIASP AQPGEAGRHA SDPVTIASPA
     QPGEAGRHAS DPVTIASPAQ PGEAGRHASD PVTIASPAQP GEAGRHASDP VTIASPAQPG
     EAGRHASDPV TSKTVWGVGI APSITTASLR AVVSAVNRAA R