ID   LEU1_PYRFU              Reviewed;         499 AA.
AC   Q8U2A2;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-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=PF0937;
OS   Pyrococcus furiosus (strain ATCC 43587 / DSM 3638 / JCM 8422 / Vc1).
OC   Archaea; Euryarchaeota; Thermococci; Thermococcales; Thermococcaceae;
OC   Pyrococcus.
OX   NCBI_TaxID=186497;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43587 / DSM 3638 / JCM 8422 / Vc1;
RX   PubMed=10430560; DOI=10.1093/genetics/152.4.1299;
RA   Maeder D.L., Weiss R.B., Dunn D.M., Cherry J.L., Gonzalez J.M.,
RA   DiRuggiero J., Robb F.T.;
RT   "Divergence of the hyperthermophilic archaea Pyrococcus furiosus and P.
RT   horikoshii inferred from complete genomic sequences.";
RL   Genetics 152:1299-1305(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: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   -!- 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; AE009950; AAL81061.1; -; Genomic_DNA.
DR   RefSeq; WP_011012073.1; NZ_CP023154.1.
DR   AlphaFoldDB; Q8U2A2; -.
DR   SMR; Q8U2A2; -.
DR   STRING; 186497.PF0937; -.
DR   EnsemblBacteria; AAL81061; AAL81061; PF0937.
DR   GeneID; 41712747; -.
DR   KEGG; pfu:PF0937; -.
DR   PATRIC; fig|186497.12.peg.993; -.
DR   eggNOG; arCOG02092; Archaea.
DR   HOGENOM; CLU_022158_0_1_2; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 10632at2157; -.
DR   PhylomeDB; Q8U2A2; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001013; 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..499
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140421"
FT   DOMAIN          5..267
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   499 AA;  54718 MW;  88029C8778D19B4B CRC64;
     MARKIKIFDT TLRDGEQTPG VSLTVEEKIE IAKQLARLNV DVIEAGFPIS SPGEFEAVKR
     IAREVRGPTI AALARAVKKD IDAAGEALKD AESKRIHTFI ATSLIHMKYK LRKTPEEVKK
     MAVEAVEYAT KYTDDIEFSA EDATRSDWNF LVEVYEAVID AGATTINVPD TVGYTTPEEF
     YELIRYLKRN ITNLNGVTIS VHCHNDLGLA VANSLSAVRA GADQVEVTVN GIGERAGNAA
     LEEVVVALDV RKDFYNVETG INLGEIARTS KLVARLTGIE VPPNKAVVGA NAFAHESGIH
     QDGVLKERTT YEIIDPRKLG FSGSKIVLGK HSGRHAFRKK LEEMGYRLSE EEINRLFAKF
     KEIADRKKGL TELDIEAIVQ EELGKGKGKY SVEVLHVISG KISTATVRVQ GDGIDKIESA
     WSSNGPIDAL FAAINRALGI DCKLKEYRVS SVTSGRDALG EVLVRVEYNG EIYVGRGLST
     DIIEASAQAY LSALNRIRR