ID   LEU1_LACLA              Reviewed;         513 AA.
AC   Q02141;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 1.
DT   25-MAY-2022, entry version 97.
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=LL1217.1;
OS   Lactococcus lactis subsp. lactis (strain IL1403) (Streptococcus lactis).
OC   Bacteria; Firmicutes; Bacilli; Lactobacillales; Streptococcaceae;
OC   Lactococcus.
OX   NCBI_TaxID=272623;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=NCDO 2118;
RX   PubMed=1400210; DOI=10.1128/jb.174.20.6580-6589.1992;
RA   Godon J.-J., Chopin M.-C., Ehrlich S.D.;
RT   "Branched-chain amino acid biosynthesis genes in Lactococcus lactis subsp.
RT   lactis.";
RL   J. Bacteriol. 174:6580-6589(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=IL1403;
RX   PubMed=8331070; DOI=10.1128/jb.175.14.4383-4390.1993;
RA   Godon J.-J., Delorme C., Bardowski J., Chopin M.-C., Ehrlich S.D.,
RA   Renault P.;
RT   "Gene inactivation in Lactococcus lactis: branched-chain amino acid
RT   biosynthesis.";
RL   J. Bacteriol. 175:4383-4390(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=IL1403;
RX   PubMed=11337471; DOI=10.1101/gr.gr-1697r;
RA   Bolotin A., Wincker P., Mauger S., Jaillon O., Malarme K., Weissenbach J.,
RA   Ehrlich S.D., Sorokin A.;
RT   "The complete genome sequence of the lactic acid bacterium Lactococcus
RT   lactis ssp. lactis IL1403.";
RL   Genome Res. 11:731-753(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).
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.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 1 subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAB81913.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC       Sequence=AE005176; Type=Erroneous termination; Note=Truncated C-terminus. The resulting protein is truncated and inactive in the dairy strain IL1403, where the leucine biosynthesis pathway is not functional.; Evidence={ECO:0000305};
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DR   EMBL; U92974; AAB81913.1; ALT_INIT; Genomic_DNA.
DR   EMBL; AE005176; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PIR; S35132; S35132.
DR   AlphaFoldDB; Q02141; -.
DR   SMR; Q02141; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000002196; 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   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..513
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140356"
FT   DOMAIN          4..266
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT   VARIANT         23
FT                   /note="S -> C (in strain: IL1403)"
FT   VARIANT         38
FT                   /note="R -> G (in strain: IL1403)"
FT   VARIANT         126
FT                   /note="R -> K (in strain: IL1403)"
FT   VARIANT         193
FT                   /note="D -> E (in strain: IL1403)"
FT   VARIANT         297
FT                   /note="G -> V (in strain: IL1403)"
FT   VARIANT         411..423
FT                   /note="EIYVSQGEGSGSV -> GAGSL (in strain: IL1403)"
FT   CONFLICT        47
FT                   /note="S -> P (in Ref. 3; AE005176)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        375
FT                   /note="H -> Q (in Ref. 2; no nucleotide entry)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   513 AA;  55803 MW;  C235351647393B2D CRC64;
     MRKIEFFDTS LRDGEQTPGV SFSISEKVTI AKQLEKWRIS VIEAGFSAAS PDSFEAVKQI
     ADSLNDTAVT ALARCVISDI DKAVEAVKGA KYPQIHVFIA TSPIHMKYKL KISPEEVLKN
     IDKCVRYARE RVEVVEFSPE DATRTELNFL LEAVQTAVDA GATYINIPDT VGYTTPEEYG
     KIFKFLIDNT KSDREIIFSP HCHDDLGMAV ANSLAAIKAG AGRVEGTVNG IGERAGNAAL
     EEIAVALHIR KDFYQAQSPL KLSETAATAE LISQFSGIAI PKNKAIVGAN AFAHESGIHQ
     DGVLKNAETY EIITPELVGI KHNSLPLGKL SGRHAFSEKL TELNIAYDDE SLAILFEKFK
     KLADKKKEIT DADIHALFTG ETVKNLAGFI LDNVQIDGHK ALVQLKNQEE EIYVSQGEGS
     GSVDAIFKAI DKVFNHQLKL ISYSVDAVTD GIDAQATTLV SVENLSTGTI FNAKGVDYDV
     LKGSAIAYMN ANVLVQKENL QGKVEQISAH DGI