ID   LEU1_MYCTO              Reviewed;         644 AA.
AC   P9WQB2; L0TGA3; O69677; P96420;
DT   16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 1.
DT   25-MAY-2022, entry version 37.
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}; OrderedLocusNames=MT3813;
OS   Mycobacterium tuberculosis (strain CDC 1551 / Oshkosh).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium; Mycobacterium tuberculosis complex.
OX   NCBI_TaxID=83331;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=CDC 1551 / Oshkosh;
RX   PubMed=12218036; DOI=10.1128/jb.184.19.5479-5490.2002;
RA   Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O.,
RA   Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K.,
RA   Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L.,
RA   Delcher A., Utterback T.R., Weidman J.F., Khouri H.M., Gill J., Mikula A.,
RA   Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M.;
RT   "Whole-genome comparison of Mycobacterium tuberculosis clinical and
RT   laboratory strains.";
RL   J. Bacteriol. 184:5479-5490(2002).
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}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAK48181.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; AE000516; AAK48181.1; ALT_INIT; Genomic_DNA.
DR   PIR; G70794; G70794.
DR   RefSeq; WP_003902547.1; NZ_KK341227.1.
DR   AlphaFoldDB; P9WQB2; -.
DR   SMR; P9WQB2; -.
DR   EnsemblBacteria; AAK48181; AAK48181; MT3813.
DR   KEGG; mtc:MT3813; -.
DR   PATRIC; fig|83331.31.peg.4106; -.
DR   HOGENOM; CLU_004588_3_2_11; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001020; 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; -; 1.
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; 1.
DR   SMART; SM00917; LeuA_dimer; 1.
DR   SUPFAM; SSF110921; SSF110921; 1.
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..644
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000426806"
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..614
FT                   /note="Insert"
FT   REGION          581..612
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   644 AA;  70114 MW;  881A9AAEA7F8FB71 CRC64;
     MTTSESPDAY TESFGAHTIV KPAGPPRVGQ PSWNPQRASS MPVNRYRPFA EEVEPIRLRN
     RTWPDRVIDR APLWCAVDLR DGNQALIDPM SPARKRRMFD LLVRMGYKEI EVGFPSASQT
     DFDFVREIIE QGAIPDDVTI QVLTQCRPEL IERTFQACSG APRAIVHFYN 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 DPVTSKTVWG VGIAPSITTA SLRAVVSAVN RAAR