ID   LEU1_METKA              Reviewed;         499 AA.
AC   Q8TYB1;
DT   26-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-2002, sequence version 1.
DT   25-MAY-2022, entry version 98.
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=MK0391;
OS   Methanopyrus kandleri (strain AV19 / DSM 6324 / JCM 9639 / NBRC 100938).
OC   Archaea; Euryarchaeota; Methanopyri; Methanopyrales; Methanopyraceae;
OC   Methanopyrus.
OX   NCBI_TaxID=190192;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AV19 / DSM 6324 / JCM 9639 / NBRC 100938;
RX   PubMed=11930014; DOI=10.1073/pnas.032671499;
RA   Slesarev A.I., Mezhevaya K.V., Makarova K.S., Polushin N.N.,
RA   Shcherbinina O.V., Shakhova V.V., Belova G.I., Aravind L., Natale D.A.,
RA   Rogozin I.B., Tatusov R.L., Wolf Y.I., Stetter K.O., Malykh A.G.,
RA   Koonin E.V., Kozyavkin S.A.;
RT   "The complete genome of hyperthermophile Methanopyrus kandleri AV19 and
RT   monophyly of archaeal methanogens.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:4644-4649(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}.
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DR   EMBL; AE009439; AAM01606.1; -; Genomic_DNA.
DR   AlphaFoldDB; Q8TYB1; -.
DR   SMR; Q8TYB1; -.
DR   STRING; 190192.MK0391; -.
DR   PRIDE; Q8TYB1; -.
DR   EnsemblBacteria; AAM01606; AAM01606; MK0391.
DR   KEGG; mka:MK0391; -.
DR   PATRIC; fig|190192.8.peg.417; -.
DR   HOGENOM; CLU_022158_0_1_2; -.
DR   OMA; NTMRMLV; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001826; 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..499
FT                   /note="Probable 2-isopropylmalate synthase"
FT                   /id="PRO_0000140451"
FT   DOMAIN          5..256
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   499 AA;  54339 MW;  B14899946601AF17 CRC64;
     MPDRVRIFDT TLRDGEQTPG VSLTVEEKVE IARKLDEFGV DTIEAGFPVA SEGEFEAVRA
     IAGEELDAEI CGLARCVKGD IDAAIDADVD CVHVFIATSD IHLRYKLEMS REEALERAIE
     GVEYASDHGV TVEFSAEDAT RTDRDYLLEV YKATVEAGAD RVNVPDTVGV MTPPEMYRLT
     AEVVDAVDVP VSVHCHNDFG MAVANSLAAV EAGAEQVHVT VNGIGERAGN ASLEQVVMAL
     KALYDIELDV RTEMLVELSR LVERLTGVVV PPNTPIVGEN AFAHESGIHS HGVIKKAETY
     EPIRPEDVGH RRRIVLGKHA GRHAIKKKLE EMGIEVTEEQ LDEIVRRVKE LGDKGKRVTE
     DDLEAIARDV VGEVPESEAA VKLEEIAVMT GNKFTPTASV RVYLDGEEHE AASTGVGSVD
     AAIRALREAI EELGMDVELK EYRLEAITGG TDALAEVTVR LEDEDGNVTT ARGAAEDIVM
     ASVKAFVRGV NRLARRRRD