ID   LEU1_CLOAB              Reviewed;         558 AA.
AC   Q97MC5;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2001, sequence version 1.
DT   25-MAY-2022, entry version 109.
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}; OrderedLocusNames=CA_C0273;
OS   Clostridium acetobutylicum (strain ATCC 824 / DSM 792 / JCM 1419 / LMG 5710
OS   / VKM B-1787).
OC   Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC   Clostridium.
OX   NCBI_TaxID=272562;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 824 / DSM 792 / JCM 1419 / LMG 5710 / VKM B-1787;
RX   PubMed=11466286; DOI=10.1128/jb.183.16.4823-4838.2001;
RA   Noelling J., Breton G., Omelchenko M.V., Makarova K.S., Zeng Q., Gibson R.,
RA   Lee H.M., Dubois J., Qiu D., Hitti J., Wolf Y.I., Tatusov R.L., Sabathe F.,
RA   Doucette-Stamm L.A., Soucaille P., Daly M.J., Bennett G.N., Koonin E.V.,
RA   Smith D.R.;
RT   "Genome sequence and comparative analysis of the solvent-producing
RT   bacterium Clostridium acetobutylicum.";
RL   J. Bacteriol. 183:4823-4838(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). {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}.
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DR   EMBL; AE001437; AAK78254.1; -; Genomic_DNA.
DR   PIR; C96933; C96933.
DR   RefSeq; NP_346914.1; NC_003030.1.
DR   RefSeq; WP_010963596.1; NC_003030.1.
DR   AlphaFoldDB; Q97MC5; -.
DR   SMR; Q97MC5; -.
DR   STRING; 272562.CA_C0273; -.
DR   EnsemblBacteria; AAK78254; AAK78254; CA_C0273.
DR   GeneID; 44996769; -.
DR   KEGG; cac:CA_C0273; -.
DR   PATRIC; fig|272562.8.peg.459; -.
DR   eggNOG; COG0119; Bacteria.
DR   HOGENOM; CLU_004588_3_0_9; -.
DR   OMA; WPDKVID; -.
DR   OrthoDB; 840579at2; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000814; 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; 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..558
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140430"
FT   DOMAIN          28..304
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   558 AA;  63443 MW;  3573DD2616A09B3F CRC64;
     MLYNKYVKYP KVKLDNREWP DKQIEKAPIW CSVDLRDGNQ ALPKPMNVDE KIKMFKMLVD
     IGFKEIEIGF PSASETEYEF TRKLIEDKLI PEDVTIQVLT QAREHLVKKT FEALKGVKTA
     IVHVYNSTSE LQRRVVFKKD KDEVKSLAIK GAQMVKKYSE YTEYSESKFV FEYSPESFTG
     TELDYALEVC EAVLNVWKPS KENKAIINLP STVEMATPNI YADQIEWFCK KLLNRESVIL
     SLHTHNDRGT CTASSELGIL AGADRVEGTL FGNGERTGNL DIMNMALNMY SQGVDPELEF
     SNLNDIVEAY EECTKMVVHE RHPYAGKLVF TAFSGSHQDA IRKGLKSLKE GKNKHWEVPY
     LAVDPHDLGR EYEEIIRINS QSGKGGTAYI MESDFGFILP KAMHPEFGKV IKKKSDELDC
     ELSPEQIFKF FKEEYLENRS PYYLKNYKIH SIQNIEEEKN TVDIEAVISV NGKDTSIEGV
     GNGPVDAFFN AMNNKKYNGC KFISYDEHAL NIGSHSKAVA YVQIESQDKK YFGVGISDNI
     DTASINAIVS ALNRSKLK