ID   LEU1_CUPMC              Reviewed;         513 AA.
AC   Q1LPX2;
DT   28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2006, sequence version 1.
DT   25-MAY-2022, entry version 100.
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=Rmet_0918;
OS   Cupriavidus metallidurans (strain ATCC 43123 / DSM 2839 / NBRC 102507 /
OS   CH34) (Ralstonia metallidurans).
OC   Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales;
OC   Burkholderiaceae; Cupriavidus.
OX   NCBI_TaxID=266264;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43123 / DSM 2839 / NBRC 102507 / CH34;
RX   PubMed=20463976; DOI=10.1371/journal.pone.0010433;
RA   Janssen P.J., Van Houdt R., Moors H., Monsieurs P., Morin N., Michaux A.,
RA   Benotmane M.A., Leys N., Vallaeys T., Lapidus A., Monchy S., Medigue C.,
RA   Taghavi S., McCorkle S., Dunn J., van der Lelie D., Mergeay M.;
RT   "The complete genome sequence of Cupriavidus metallidurans strain CH34, a
RT   master survivalist in harsh and anthropogenic environments.";
RL   PLoS ONE 5:E10433-E10433(2010).
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; CP000352; ABF07804.1; -; Genomic_DNA.
DR   RefSeq; WP_008643333.1; NC_007973.1.
DR   AlphaFoldDB; Q1LPX2; -.
DR   SMR; Q1LPX2; -.
DR   STRING; 266264.Rmet_0918; -.
DR   EnsemblBacteria; ABF07804; ABF07804; Rmet_0918.
DR   GeneID; 60825405; -.
DR   KEGG; rme:Rmet_0918; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_022158_0_1_4; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 840579at2; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000002429; 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_1000149254"
FT   DOMAIN          5..268
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   513 AA;  55793 MW;  9197ECBBEA35B1F2 CRC64;
     MSDKLIIFDT TLRDGEQSPG ASMTREEKIR IARQLERLKV DVIEAGFAAS SNGDFEAIRS
     IAQVVKDSTI CSLARANDKD IARAAEALKP ANSFRIHTFI ATSALHMEKK LRMTPDQVYE
     QARLAVRFAR QFTDDIEFSP EDGSRSDMDF LCRVLEGVIA EGATTINLPD TVGYAVPEGY
     AELIRSVRER IPNSDKAVWS VHCHNDLGMA VANSLAAVKL GGARQIECTI NGLGERAGNT
     SLEEVVMAVK TRRDYFNMDV GIDTTQIVPA SKLVSQITGF VVQPNKAVVG ANAFAHASGI
     HQDGVLKARD TYEIMRAEDV GWTANKIVLG KLSGRNAFKQ RLQELGVQLE SEAEINAAFA
     RFKELADQKA EIFDEDIMAI VSDEEQEHAN EHYRFISLSQ RSETGERPHA RVVFNIDGSE
     QTGEAEGNGP VDATLHAIEG KVNSGAELVL YSVNAITAGT QAQGEVTVRL SKAGRIVNGV
     GTDPDIVAAS AKAYLAALNK LHDKAVQKIN PQI