ID   LEU1_MYCLE              Reviewed;         607 AA.
AC   Q9CB76; O69523;
DT   29-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2001, sequence version 1.
DT   03-AUG-2022, entry version 113.
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=ML2324;
GN   ORFNames=MLCB2407.26c;
OS   Mycobacterium leprae (strain TN).
OC   Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC   Mycobacterium.
OX   NCBI_TaxID=272631;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=TN;
RX   PubMed=11234002; DOI=10.1038/35059006;
RA   Cole S.T., Eiglmeier K., Parkhill J., James K.D., Thomson N.R.,
RA   Wheeler P.R., Honore N., Garnier T., Churcher C.M., Harris D.E.,
RA   Mungall K.L., Basham D., Brown D., Chillingworth T., Connor R.,
RA   Davies R.M., Devlin K., Duthoy S., Feltwell T., Fraser A., Hamlin N.,
RA   Holroyd S., Hornsby T., Jagels K., Lacroix C., Maclean J., Moule S.,
RA   Murphy L.D., Oliver K., Quail M.A., Rajandream M.A., Rutherford K.M.,
RA   Rutter S., Seeger K., Simon S., Simmonds M., Skelton J., Squares R.,
RA   Squares S., Stevens K., Taylor K., Whitehead S., Woodward J.R.,
RA   Barrell B.G.;
RT   "Massive gene decay in the leprosy bacillus.";
RL   Nature 409:1007-1011(2001).
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; AL023596; CAA19166.1; -; Genomic_DNA.
DR   EMBL; AL583925; CAC31840.1; -; Genomic_DNA.
DR   PIR; H87199; H87199.
DR   AlphaFoldDB; Q9CB76; -.
DR   SMR; Q9CB76; -.
DR   STRING; 272631.ML2324; -.
DR   PRIDE; Q9CB76; -.
DR   EnsemblBacteria; CAC31840; CAC31840; CAC31840.
DR   KEGG; mle:ML2324; -.
DR   Leproma; ML2324; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_004588_3_2_11; -.
DR   OMA; WPDKVID; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000806; 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; Reference proteome; Transferase.
FT   CHAIN           1..607
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140435"
FT   DOMAIN          75..349
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   COMPBIAS        1..16
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   607 AA;  66898 MW;  5C5744B8727A84D1 CRC64;
     MASFSESLSQ DPADAYKSAP SITKPMGPPS PGQPQWNPQR ATSMPVFRYR PFAKEVEPIR
     LVDRTWPDRV IDCAPLWCAV DLRDGNQALI DPMSPICKRR MFDLLVRMGY KEIEVGFPSA
     SQTDFDFVRE IITDGTIPDD VTIQVLTQCR PELIERTFEA CENASRVIVH FYNSTSILQR
     RVVFRADQAT VKAIATDGAR KCVEEAFKYP GTHWRFEYSP ESYTGTELEY AKQVCDAVGE
     VIQPTPDNPI IFNLPATVEM ATPNVYADSI EWMSRNLANR ESVILSLHPH NDRGTAVAAA
     ELGYHAGADR IEGCLFGNGE RTGNVCLVTL GLNLFSRGVD PQIDFSNIDE IRRTVEYCNK
     LRVHERHPYG GDLVYTAFSG SHQDAINKGL DQMKIDADAA DSDVDDILWQ VPYLPIDPRD
     VGRTYEAVIR VNSQSGKGGV AYIMKADHGL ELPRRLQIEF SRAIQKISEG EGGEITPTEM
     WDVFFEEYLS PVQPLERIKQ RVNAAEEDGG STSIAATVKI NGEETEISGV GNGPLAAFID
     ALGHVGLQVA VLDYSEHAMN AGDDAQAAAY VEASVHGHTA WGVGIAPSIT TASLRAVVSA
     VNRAMPR