ID   LEU1_METAC              Reviewed;         515 AA.
AC   Q8THA5;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   25-MAY-2022, entry version 105.
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=MA_4615;
OS   Methanosarcina acetivorans (strain ATCC 35395 / DSM 2834 / JCM 12185 /
OS   C2A).
OC   Archaea; Euryarchaeota; Stenosarchaea group; Methanomicrobia;
OC   Methanosarcinales; Methanosarcinaceae; Methanosarcina.
OX   NCBI_TaxID=188937;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 35395 / DSM 2834 / JCM 12185 / C2A;
RX   PubMed=11932238; DOI=10.1101/gr.223902;
RA   Galagan J.E., Nusbaum C., Roy A., Endrizzi M.G., Macdonald P., FitzHugh W.,
RA   Calvo S., Engels R., Smirnov S., Atnoor D., Brown A., Allen N., Naylor J.,
RA   Stange-Thomann N., DeArellano K., Johnson R., Linton L., McEwan P.,
RA   McKernan K., Talamas J., Tirrell A., Ye W., Zimmer A., Barber R.D.,
RA   Cann I., Graham D.E., Grahame D.A., Guss A.M., Hedderich R.,
RA   Ingram-Smith C., Kuettner H.C., Krzycki J.A., Leigh J.A., Li W., Liu J.,
RA   Mukhopadhyay B., Reeve J.N., Smith K., Springer T.A., Umayam L.A.,
RA   White O., White R.H., de Macario E.C., Ferry J.G., Jarrell K.F., Jing H.,
RA   Macario A.J.L., Paulsen I.T., Pritchett M., Sowers K.R., Swanson R.V.,
RA   Zinder S.H., Lander E., Metcalf W.W., Birren B.;
RT   "The genome of Methanosarcina acetivorans reveals extensive metabolic and
RT   physiological diversity.";
RL   Genome Res. 12:532-542(2002).
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}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; AE010299; AAM07951.1; -; Genomic_DNA.
DR   RefSeq; WP_011024485.1; NC_003552.1.
DR   AlphaFoldDB; Q8THA5; -.
DR   SMR; Q8THA5; -.
DR   STRING; 188937.MA_4615; -.
DR   EnsemblBacteria; AAM07951; AAM07951; MA_4615.
DR   GeneID; 1476509; -.
DR   KEGG; mac:MA_4615; -.
DR   HOGENOM; CLU_022158_0_1_2; -.
DR   InParanoid; Q8THA5; -.
DR   OMA; NTMRMLV; -.
DR   OrthoDB; 10632at2157; -.
DR   PhylomeDB; Q8THA5; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000002487; 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   3: Inferred from homology;
KW   Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW   Leucine biosynthesis; Reference proteome; Transferase.
FT   CHAIN           1..515
FT                   /note="Probable 2-isopropylmalate synthase"
FT                   /id="PRO_0000140409"
FT   DOMAIN          20..271
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   515 AA;  55693 MW;  A1FAE52E5FF5C90A CRC64;
     MYTLKEGIDF YIEPMQNKKV TVFDTTLRDG EQTPGVSLTS SQKLEISRQL DKLGVDIIEA
     GFPISSEGDK ESVKSISNAG LETTVCGLAR VLKKDIDACF ESDVGLVHTF VPTSDVQRIY
     TIKKSQEEVI QLAVEAVQYI KDHGLKCMFS AMDATRTDPA YLIEVFKAVQ EAGCDIINVP
     DTVGVMVPSA MYRQIKDIAA EITIPIDVHC HNDFGLAVAN SLMAVEAGAS QVQVTINGIG
     ERAGNADLAQ TVMSLASIYG IKTNIRTEYL VETSKMIENY TGIRLPPNTP VVGQNAFSHE
     SGIHSQGVLE KSDTFEPGIM TPEMVGHRRR IVLGKHTGKH AVKQSLESAG VKTSENQLDE
     IVLRIKEIAN KGKQITDADL YAVASAVLGK ASSEEELIKL KEVSVMTGNI LTPTAVVKAD
     IEGKEIIAAK TGVGPVDAAL KAVRDILGES NHFRLQEFRI DAITGGADAL ADVYIGLENE
     KGRIVTARSA NPDIVMASVE ALINAMNLLY KKEKS