ID   LEU1_METJA              Reviewed;         518 AA.
AC   Q58595;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   25-MAY-2022, entry version 112.
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=MJ1195;
OS   Methanocaldococcus jannaschii (strain ATCC 43067 / DSM 2661 / JAL-1 / JCM
OS   10045 / NBRC 100440) (Methanococcus jannaschii).
OC   Archaea; Euryarchaeota; Methanomada group; Methanococci; Methanococcales;
OC   Methanocaldococcaceae; Methanocaldococcus.
OX   NCBI_TaxID=243232;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 43067 / DSM 2661 / JAL-1 / JCM 10045 / NBRC 100440;
RX   PubMed=8688087; DOI=10.1126/science.273.5278.1058;
RA   Bult C.J., White O., Olsen G.J., Zhou L., Fleischmann R.D., Sutton G.G.,
RA   Blake J.A., FitzGerald L.M., Clayton R.A., Gocayne J.D., Kerlavage A.R.,
RA   Dougherty B.A., Tomb J.-F., Adams M.D., Reich C.I., Overbeek R.,
RA   Kirkness E.F., Weinstock K.G., Merrick J.M., Glodek A., Scott J.L.,
RA   Geoghagen N.S.M., Weidman J.F., Fuhrmann J.L., Nguyen D., Utterback T.R.,
RA   Kelley J.M., Peterson J.D., Sadow P.W., Hanna M.C., Cotton M.D.,
RA   Roberts K.M., Hurst M.A., Kaine B.P., Borodovsky M., Klenk H.-P.,
RA   Fraser C.M., Smith H.O., Woese C.R., Venter J.C.;
RT   "Complete genome sequence of the methanogenic archaeon, Methanococcus
RT   jannaschii.";
RL   Science 273:1058-1073(1996).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=9665716; DOI=10.1021/bi980662p;
RA   Howell D.M., Harich K., Xu H., White R.H.;
RT   "Alpha-keto acid chain elongation reactions involved in the biosynthesis of
RT   coenzyme B (7-mercaptoheptanoyl threonine phosphate) in methanogenic
RT   Archaea.";
RL   Biochemistry 37:10108-10117(1998).
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).
CC       {ECO:0000269|PubMed:9665716}.
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:0000269|PubMed:9665716};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000269|PubMed:9665716}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. {ECO:0000305}.
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DR   EMBL; L77117; AAB99199.1; -; Genomic_DNA.
DR   PIR; B64449; B64449.
DR   RefSeq; WP_010870707.1; NC_000909.1.
DR   AlphaFoldDB; Q58595; -.
DR   SMR; Q58595; -.
DR   STRING; 243232.MJ_1195; -.
DR   EnsemblBacteria; AAB99199; AAB99199; MJ_1195.
DR   GeneID; 1452090; -.
DR   KEGG; mja:MJ_1195; -.
DR   eggNOG; arCOG02092; Archaea.
DR   HOGENOM; CLU_022158_0_1_2; -.
DR   InParanoid; Q58595; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 10632at2157; -.
DR   PhylomeDB; Q58595; -.
DR   BRENDA; 2.3.3.13; 3260.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000000805; Chromosome.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IEA:UniProtKB-EC.
DR   GO; GO:0019298; P:coenzyme B biosynthetic process; IBA:GO_Central.
DR   GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.20.20.70; -; 1.
DR   Gene3D; 3.30.160.270; -; 1.
DR   InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR   InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR011830; LEU1_arch.
DR   InterPro; IPR036230; LeuA_allosteric_dom_sf.
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; TIGR02090; LEU1_arch; 1.
DR   PROSITE; PS00815; AIPM_HOMOCIT_SYNTH_1; 1.
DR   PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR   PROSITE; PS50991; PYR_CT; 1.
PE   1: Evidence at protein level;
KW   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW   Leucine biosynthesis; Reference proteome; Transferase.
FT   CHAIN           1..518
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000140411"
FT   DOMAIN          24..275
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   518 AA;  56620 MW;  604AB61B41E607A4 CRC64;
     MIIYREENEI IKKALENLNI PDRVYIFDTT LRDGEQTPGV SLTPEEKIDI AIKLDDLGVD
     VIEAGFPVSS LGEQEAIKKI CSLNLDAEIC GLARAVKKDI DVAIDCGVDR IHTFIATSPL
     HRKYKLKKSK EEIIDIAVDA IEYIKEHGIR VEFSAEDATR TEIDYLIEVY KKAVDAGADI
     INVPDTVGVM IPRAMYYLIN ELKKEIKVPI SVHCHNDFGL AVANSLAAVE AGAEQVHCTI
     NGLGERGGNA ALEEVVMSLM SIYGVKTNIK TQKLYEISQL VSKYTEIKVQ PNKAIVGENA
     FAHESGIHAH GVLAHALTYE PIPPELVGQK RKIILGKHTG THAIEAKLKE LGIEVGKDIN
     KDQFDEIVKR IKALGDKGKR VTDRDVEAIV EDVVGKLAKK DRVVELEQIA VMTGNRVIPT
     ASVALKIEEE IKKSSAIGVG PVDAAVKAIQ KAIGEKIKLK EYHINAITGG TDALAEVIVT
     LEGYGREITT KAASEDIVRA SVEAVIDGIN KILAKREK