ID   LEU1_CORGL              Reviewed;         616 AA.
AC   P42455;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1995, sequence version 1.
DT   03-AUG-2022, entry version 135.
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=Cgl0248, cg0303;
OS   Corynebacterium glutamicum (strain ATCC 13032 / DSM 20300 / BCRC 11384 /
OS   JCM 1318 / LMG 3730 / NCIMB 10025).
OC   Bacteria; Actinobacteria; Corynebacteriales; Corynebacteriaceae;
OC   Corynebacterium.
OX   NCBI_TaxID=196627;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC   10025;
RX   PubMed=8117072; DOI=10.1128/aem.60.1.133-140.1994;
RA   Patek M., Krumbach K., Eggeling L., Sahm H.;
RT   "Leucine synthesis in Corynebacterium glutamicum: enzyme activities,
RT   structure of leuA, and effect of leuA inactivation on lysine synthesis.";
RL   Appl. Environ. Microbiol. 60:133-140(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC   10025;
RX   PubMed=12743753; DOI=10.1007/s00253-003-1328-1;
RA   Ikeda M., Nakagawa S.;
RT   "The Corynebacterium glutamicum genome: features and impacts on
RT   biotechnological processes.";
RL   Appl. Microbiol. Biotechnol. 62:99-109(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 13032 / DSM 20300 / BCRC 11384 / JCM 1318 / LMG 3730 / NCIMB
RC   10025;
RX   PubMed=12948626; DOI=10.1016/s0168-1656(03)00154-8;
RA   Kalinowski J., Bathe B., Bartels D., Bischoff N., Bott M., Burkovski A.,
RA   Dusch N., Eggeling L., Eikmanns B.J., Gaigalat L., Goesmann A.,
RA   Hartmann M., Huthmacher K., Kraemer R., Linke B., McHardy A.C., Meyer F.,
RA   Moeckel B., Pfefferle W., Puehler A., Rey D.A., Rueckert C., Rupp O.,
RA   Sahm H., Wendisch V.F., Wiegraebe I., Tauch A.;
RT   "The complete Corynebacterium glutamicum ATCC 13032 genome sequence and its
RT   impact on the production of L-aspartate-derived amino acids and vitamins.";
RL   J. Biotechnol. 104:5-25(2003).
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=CAA50295.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X70959; CAA50295.1; ALT_INIT; Genomic_DNA.
DR   EMBL; BA000036; BAB97641.1; -; Genomic_DNA.
DR   EMBL; BX927148; CAF18819.1; -; Genomic_DNA.
DR   RefSeq; NP_599502.2; NC_003450.3.
DR   RefSeq; WP_015439406.1; NC_006958.1.
DR   AlphaFoldDB; P42455; -.
DR   SMR; P42455; -.
DR   STRING; 196627.cg0303; -.
DR   KEGG; cgb:cg0303; -.
DR   KEGG; cgl:Cgl0248; -.
DR   PATRIC; fig|196627.13.peg.253; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_004588_3_2_11; -.
DR   OMA; WPDKVID; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000582; 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..616
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140432"
FT   DOMAIN          67..341
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT   REGION          1..34
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   616 AA;  68188 MW;  6B0CB8BDC6F91A41 CRC64;
     MSPNDAFISA PAKIETPVGP RNEGQPAWNK QRGSSMPVNR YMPFEVEVED ISLPDRTWPD
     KKITVAPQWC AVDLRDGNQA LIDPMSPERK RRMFELLVQM GFKEIEVGFP SASQTDFDFV
     REIIEKGMIP DDVTIQVLVQ AREHLIRRTF EACEGAKNVI VHFYNSTSIL QRNVVFRMDK
     VQVKKLATDA AELIKTIAQD YPDTNWRWQY SPESFTGTEV EYAKEVVDAV VEVMDPTPEN
     PMIINLPSTV EMITPNVYAD SIEWMHRNLN RRDSIILSLH PHNDRGTGVG AAELGYMAGA
     DRIEGCLFGN GERTGNVCLV TLALNMLTQG VDPQLDFTDI RQIRSTVEYC NQLRVPERHP
     YGGDLVFTAF SGSHQDAVNK GLDAMAAKVQ PGASSTEVSW EQLRDTEWEV PYLPIDPKDV
     GRDYEAVIRV NSQSGKGGVA YIMKTDHGLQ IPRSMQVEFS TVVQNVTDAE GGEVNSKAMW
     DIFATEYLER TAPVEQIALR VENAQTENED ASITAELIHN GKDVTVDGRG NGPLAAYANA
     LEKLGIDVEI QEYNQHARTS GDDAEAAAYV LAEVNGRKVW GVGIAGSITY ASLKAVTSAV
     NRALDVNHEA VLAGGV