ID   LEU1_THEMA              Reviewed;         513 AA.
AC   Q9WZ23;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1999, sequence version 1.
DT   25-MAY-2022, entry version 127.
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=TM_0553;
OS   Thermotoga maritima (strain ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826
OS   / MSB8).
OC   Bacteria; Thermotogae; Thermotogales; Thermotogaceae; Thermotoga.
OX   NCBI_TaxID=243274;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43589 / DSM 3109 / JCM 10099 / NBRC 100826 / MSB8;
RX   PubMed=10360571; DOI=10.1038/20601;
RA   Nelson K.E., Clayton R.A., Gill S.R., Gwinn M.L., Dodson R.J., Haft D.H.,
RA   Hickey E.K., Peterson J.D., Nelson W.C., Ketchum K.A., McDonald L.A.,
RA   Utterback T.R., Malek J.A., Linher K.D., Garrett M.M., Stewart A.M.,
RA   Cotton M.D., Pratt M.S., Phillips C.A., Richardson D.L., Heidelberg J.F.,
RA   Sutton G.G., Fleischmann R.D., Eisen J.A., White O., Salzberg S.L.,
RA   Smith H.O., Venter J.C., Fraser C.M.;
RT   "Evidence for lateral gene transfer between Archaea and Bacteria from
RT   genome sequence of Thermotoga maritima.";
RL   Nature 399:323-329(1999).
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:0000250}.
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. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 1 subfamily. {ECO:0000305}.
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DR   EMBL; AE000512; AAD35638.1; -; Genomic_DNA.
DR   PIR; G72362; G72362.
DR   RefSeq; NP_228363.1; NC_000853.1.
DR   RefSeq; WP_004081333.1; NZ_CP011107.1.
DR   AlphaFoldDB; Q9WZ23; -.
DR   SMR; Q9WZ23; -.
DR   STRING; 243274.THEMA_01910; -.
DR   EnsemblBacteria; AAD35638; AAD35638; TM_0553.
DR   KEGG; tma:TM0553; -.
DR   eggNOG; COG0119; Bacteria.
DR   InParanoid; Q9WZ23; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 840579at2; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000008183; Chromosome.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IBA:GO_Central.
DR   GO; GO:0009098; P:leucine biosynthetic process; IBA:GO_Central.
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_0000140391"
FT   DOMAIN          4..268
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   513 AA;  56805 MW;  08EBF526E5BD4502 CRC64;
     MRRIKIFDTT LRDGEQSPGA SMSIEEKVEM ALMLEDLGVD LIEAGFPVSS PVQFEAVKRV
     ASAVQKPIVV GLARCVEKDI DAAYEALKDR PKDKRMIHVF IATSPIHRKY KLRMEKEEIL
     ERIRRYVGYA KQFFDLVEFS AEDASRTEVP FLIEAYKTAI EAGATTINVP DTVGYALPDE
     FGELIKTLRE GVPGIENVDL SVHCHNDLGL AVANSLAAVQ NGATQVEVTL NGIGERAGNC
     ALEEFVMILK VRKDKLPYET GIKTELIYPA SRLLTHITGL IPSRNKPIVG ENVFLHESGI
     HQDGVLKHRE TYEIMKPSDI GRSSETLVLG RHSGKHALRK KLETYGIKLD EETFQKVFEK
     FTELADRKKE VYDDDLFSIV SEVLREPING YKLVHFHVHT GNTLLPTAAV VLQVGNEKRE
     AAEAGNGPVD AIFKAIDKAL GIQPKLEEYI IQAVGTGKNA QGEVKLTLRI DNELYSGRGV
     STDIVEASAI AYINAINKYL IAKGLLRKNG GAE