ID   LEU1_METTH              Reviewed;         505 AA.
AC   O27525;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   25-MAY-2022, entry version 114.
DE   RecName: Full=Probable 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=MTH_1481;
OS   Methanothermobacter thermautotrophicus (strain ATCC 29096 / DSM 1053 / JCM
OS   10044 / NBRC 100330 / Delta H) (Methanobacterium thermoautotrophicum).
OC   Archaea; Euryarchaeota; Methanomada group; Methanobacteria;
OC   Methanobacteriales; Methanobacteriaceae; Methanothermobacter.
OX   NCBI_TaxID=187420;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 29096 / DSM 1053 / JCM 10044 / NBRC 100330 / Delta H;
RX   PubMed=9371463; DOI=10.1128/jb.179.22.7135-7155.1997;
RA   Smith D.R., Doucette-Stamm L.A., Deloughery C., Lee H.-M., Dubois J.,
RA   Aldredge T., Bashirzadeh R., Blakely D., Cook R., Gilbert K., Harrison D.,
RA   Hoang L., Keagle P., Lumm W., Pothier B., Qiu D., Spadafora R., Vicare R.,
RA   Wang Y., Wierzbowski J., Gibson R., Jiwani N., Caruso A., Bush D.,
RA   Safer H., Patwell D., Prabhakar S., McDougall S., Shimer G., Goyal A.,
RA   Pietrovski S., Church G.M., Daniels C.J., Mao J.-I., Rice P., Noelling J.,
RA   Reeve J.N.;
RT   "Complete genome sequence of Methanobacterium thermoautotrophicum deltaH:
RT   functional analysis and comparative genomics.";
RL   J. Bacteriol. 179:7135-7155(1997).
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   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. {ECO:0000305}.
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DR   EMBL; AE000666; AAB85956.1; -; Genomic_DNA.
DR   PIR; D69064; D69064.
DR   RefSeq; WP_010877091.1; NC_000916.1.
DR   AlphaFoldDB; O27525; -.
DR   SMR; O27525; -.
DR   STRING; 187420.MTH_1481; -.
DR   EnsemblBacteria; AAB85956; AAB85956; MTH_1481.
DR   GeneID; 24854587; -.
DR   KEGG; mth:MTH_1481; -.
DR   PATRIC; fig|187420.15.peg.1443; -.
DR   HOGENOM; CLU_022158_0_1_2; -.
DR   OMA; NTMRMLV; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000005223; Chromosome.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IEA:UniProtKB-EC.
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   3: Inferred from homology;
KW   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW   Leucine biosynthesis; Reference proteome; Transferase.
FT   CHAIN           1..505
FT                   /note="Probable 2-isopropylmalate synthase"
FT                   /id="PRO_0000140417"
FT   DOMAIN          16..265
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   505 AA;  54674 MW;  7DEDE80E144C5DA5 CRC64;
     MYIEEVKGEM NLPENVRIFD TTLRDGEQTP GVALTVEEKT GIARKLDALG VDTIEAGFPA
     ASPGEMNSIR RIVELGLEAN ICGLARVLRE DIDAAIDCGV DYIHTFIGTS PLHREYKLKM
     SPDEIIDRAV FGVEYAAEHG LKVEFSAEDA TRTEFDYLVE VYRAAEDAGA EIINVPDTVG
     VMIPRAMNHL VSRLKEELRV PISVHCHNDF GLAVANSLAA VEAGASQVHA TVNGLGERAG
     NAALEEVVMA LITRYDLPVD IRTVELVNIS EFVSKITGVR MPPNKAIVGE NAFAHEAGIH
     VHGVLEKAET YEPITPEMVG HKRRIVLGKH TGANALRSKL QEYGIEMKEE QFCTLYEQVK
     RLGDKGKRIT DADLRAMAVT ILGKASREIV KLEGIAVMTG ESVMPTATVK LRIGDEVKTT
     SMTGVGPVDA AINAIQSLVS ETADIELDEY NIEAITGGTN ALAEVFVVMS DGEGNKATGR
     STREDIVMAS VEAVLDAINK ILSLK