ID   LEU1_STAAW              Reviewed;         509 AA.
AC   P58899;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   26-JUL-2002, sequence version 1.
DT   25-MAY-2022, entry version 104.
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=MW1981;
OS   Staphylococcus aureus (strain MW2).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=196620;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=MW2;
RX   PubMed=12044378; DOI=10.1016/s0140-6736(02)08713-5;
RA   Baba T., Takeuchi F., Kuroda M., Yuzawa H., Aoki K., Oguchi A., Nagai Y.,
RA   Iwama N., Asano K., Naimi T., Kuroda H., Cui L., Yamamoto K., Hiramatsu K.;
RT   "Genome and virulence determinants of high virulence community-acquired
RT   MRSA.";
RL   Lancet 359:1819-1827(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_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; BA000033; BAB95846.1; -; Genomic_DNA.
DR   RefSeq; WP_000094582.1; NC_003923.1.
DR   AlphaFoldDB; P58899; -.
DR   SMR; P58899; -.
DR   EnsemblBacteria; BAB95846; BAB95846; BAB95846.
DR   KEGG; sam:MW1981; -.
DR   HOGENOM; CLU_022158_0_1_9; -.
DR   OMA; NTMRMLV; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000418; 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; 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; 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..509
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140383"
FT   DOMAIN          5..267
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   509 AA;  55617 MW;  E4D27994C18FA369 CRC64;
     MSSHIQIFDT TLRDGEQTPG VNFTFDERLR IALQLEKWGV DVIEAGFPAS STGSFKSVQA
     IAQTLTTTAV CGLARCKKSD IDAVYEATKD AAKPVVHVFI ATSPIHLEHK LKMSQEDVLA
     SIKEHVTYAK QLFDVVQFSP EDATRTELPF LVKCVQTAVD AGATVINIPD TVGYSYHDEY
     AHIFKTLTES VTSSNEIIYS AHCHDDLGMA VSNSLAAIEG GARRIEGTVN GIGERAGNAA
     LEEVALALYV RNDHYGAQTA LNLEETKKTS DLISRYAGIR VPRNKAIVGQ NAFSHESGIH
     QDGVLKHRET YEIMTPQLVG VSTTELPLGK LSGKHAFSEK LKALGYGIDK EAQIDLFKQF
     KAIADKKKSV SDRDIHAIIQ GSEHEHQALY KLETLQLQYV SSGLQSAVVV VKDKEGHIYQ
     DSSIGTGSIV AIYNAVDRIF QKETELIDYR INSVTEGTDA QAEVHVNLLI EGKTVNGFGI
     DHDILQASCK AYVEAHAKFA AENVEKVGN