ID   LEU1_STAES              Reviewed;         511 AA.
AC   Q8CNL3;
DT   31-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   25-MAY-2022, entry version 108.
DE   RecName: Full=2-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025};
DE            EC=2.3.3.13 {ECO:0000255|HAMAP-Rule:MF_01025};
DE   AltName: Full=Alpha-IPM synthase {ECO:0000255|HAMAP-Rule:MF_01025};
DE   AltName: Full=Alpha-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025};
GN   Name=leuA {ECO:0000255|HAMAP-Rule:MF_01025}; OrderedLocusNames=SE_1658;
OS   Staphylococcus epidermidis (strain ATCC 12228 / FDA PCI 1200).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=176280;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 12228 / FDA PCI 1200;
RX   PubMed=12950922; DOI=10.1046/j.1365-2958.2003.03671.x;
RA   Zhang Y.-Q., Ren S.-X., Li H.-L., Wang Y.-X., Fu G., Yang J., Qin Z.-Q.,
RA   Miao Y.-G., Wang W.-Y., Chen R.-S., Shen Y., Chen Z., Yuan Z.-H.,
RA   Zhao G.-P., Qu D., Danchin A., Wen Y.-M.;
RT   "Genome-based analysis of virulence genes in a non-biofilm-forming
RT   Staphylococcus epidermidis strain (ATCC 12228).";
RL   Mol. Microbiol. 49:1577-1593(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_01025}.
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_01025};
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_01025}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01025}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_01025}.
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DR   EMBL; AE015929; AAO05257.1; -; Genomic_DNA.
DR   RefSeq; NP_765213.1; NC_004461.1.
DR   RefSeq; WP_001830007.1; NZ_WBME01000022.1.
DR   AlphaFoldDB; Q8CNL3; -.
DR   SMR; Q8CNL3; -.
DR   STRING; 176280.SE_1658; -.
DR   EnsemblBacteria; AAO05257; AAO05257; SE_1658.
DR   GeneID; 50018243; -.
DR   KEGG; sep:SE_1658; -.
DR   PATRIC; fig|176280.10.peg.1622; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_022158_0_1_9; -.
DR   OMA; NTMRMLV; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001411; 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; 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..511
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140384"
FT   DOMAIN          5..267
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   511 AA;  56546 MW;  02B4D70ED817D55E CRC64;
     MEEHIQIFDT TLRDGEQTPG VNFTFDERLK IAKQLEKWGV DVLEAGFPAS STGSFKSVEA
     IAKTLTTTAV CGLARCKKSD IDAVYEATKE AVKPQVHVFI ATSPIHLEHK LKMTQDEVLT
     SIKEHVSYAK QFFEVVQFSP EDATRTEIPF LIECVQTAIN AGATIINIPD TVGFSYPTEY
     GEIFKQLTQA VKSNSKIIFS AHCHDDLGMA VANSLAAIEG GARRIEGTVN GIGERAGNAS
     LEEVALALYV RKDHYGLESQ INLEETKKTS DLISRYAGIR VPRNKAIVGQ NAFSHESGIH
     QDGVLKHRET YEIMTPQLVG VNTTELPLGK LSGKHAFAEK LKALGYEIKL EDQVTLFKQF
     KEIADKKKNV SDRDIHAIIH GSEHEHNAIF QLDNLQLQYV SKGLQSAVVV IKERNGQVKQ
     DSSIGTGSIV AIYNAVDRIF KKDAELIDYR IDSVTEGTDA QAEVHVRIII NHIEVTGIGI
     DHDILKASCK AYIDAHAKYI SEYELKEGIR T