ID   LEU1_SULAC              Reviewed;         386 AA.
AC   Q4JA78;
DT   16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT   02-AUG-2005, sequence version 1.
DT   25-MAY-2022, entry version 76.
DE   RecName: Full=2-isopropylmalate synthase {ECO:0000305|PubMed:31330039};
DE            Short=IPMS {ECO:0000303|PubMed:31330039};
DE            EC=2.3.3.13 {ECO:0000269|PubMed:31330039};
DE   AltName: Full=Alpha-isopropylmalate synthase;
DE            Short=Alpha-IPM synthase;
GN   OrderedLocusNames=Saci_0940 {ECO:0000312|EMBL:AAY80302.1};
OS   Sulfolobus acidocaldarius (strain ATCC 33909 / DSM 639 / JCM 8929 / NBRC
OS   15157 / NCIMB 11770).
OC   Archaea; Crenarchaeota; Thermoprotei; Sulfolobales; Sulfolobaceae;
OC   Sulfolobus.
OX   NCBI_TaxID=330779;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 33909 / DSM 639 / JCM 8929 / NBRC 15157 / NCIMB 11770;
RX   PubMed=15995215; DOI=10.1128/jb.187.14.4992-4999.2005;
RA   Chen L., Bruegger K., Skovgaard M., Redder P., She Q., Torarinsson E.,
RA   Greve B., Awayez M., Zibat A., Klenk H.-P., Garrett R.A.;
RT   "The genome of Sulfolobus acidocaldarius, a model organism of the
RT   Crenarchaeota.";
RL   J. Bacteriol. 187:4992-4999(2005).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, ACTIVITY REGULATION,
RP   PATHWAY, AND DISRUPTION PHENOTYPE.
RX   PubMed=31330039; DOI=10.1002/1873-3468.13550;
RA   Suzuki T., Akiyama N., Yoshida A., Tomita T., Lassak K., Haurat M.F.,
RA   Okada T., Takahashi K., Albers S.V., Kuzuyama T., Nishiyama M.;
RT   "Biochemical characterization of archaeal homocitrate synthase from
RT   Sulfolobus acidocaldarius.";
RL   FEBS Lett. 594:126-134(2020).
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). Carries out the first
CC       step of the leucine biosynthesis pathway. Also displays a low
CC       citramalate synthase activity, using pyruvate as substrate, but is
CC       unable to use 2-oxoglutarate. {ECO:0000269|PubMed:31330039}.
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:31330039};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21525;
CC         Evidence={ECO:0000269|PubMed:31330039};
CC   -!- ACTIVITY REGULATION: Is not inhibited by leucine.
CC       {ECO:0000269|PubMed:31330039}.
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000269|PubMed:31330039}.
CC   -!- DISRUPTION PHENOTYPE: Cells lacking this gene exhibit very retarded
CC       growth in MM and the addition of isoleucine does not affect the growth
CC       of this mutant, whereas the addition of leucine appears to improve
CC       growth in MM. {ECO:0000269|PubMed:31330039}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. {ECO:0000305}.
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DR   EMBL; CP000077; AAY80302.1; -; Genomic_DNA.
DR   RefSeq; WP_011277804.1; NC_007181.1.
DR   AlphaFoldDB; Q4JA78; -.
DR   SMR; Q4JA78; -.
DR   STRING; 330779.Saci_0940; -.
DR   EnsemblBacteria; AAY80302; AAY80302; Saci_0940.
DR   GeneID; 3473050; -.
DR   KEGG; sai:Saci_0940; -.
DR   PATRIC; fig|330779.12.peg.901; -.
DR   eggNOG; arCOG02092; Archaea.
DR   HOGENOM; CLU_022158_4_2_2; -.
DR   OMA; NTMRMLV; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001018; 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   InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR011830; LEU1_arch.
DR   InterPro; IPR000891; PYR_CT.
DR   Pfam; PF00682; HMGL-like; 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   Acyltransferase; Amino-acid biosynthesis;
KW   Branched-chain amino acid biosynthesis; Leucine biosynthesis;
KW   Reference proteome; Transferase.
FT   CHAIN           1..386
FT                   /note="2-isopropylmalate synthase"
FT                   /id="PRO_0000448051"
FT   DOMAIN          12..265
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   386 AA;  42271 MW;  F18DADB39D54F140 CRC64;
     MGCLFSVNSK KVRIFDTTLR DGEQAPGIDL TVDQKIRVAK RLAELGVDVI EAGFPASSDG
     EFEATKKILS EIGDQVEVTG LSRSVKQDID RTIDTGLSSI HIFIATSDIH LKYKLKMTRE
     EVLNRIYESV RYAKDHGLIV EYSPEDATRS DEEFLLKAVK TAIDAGADRI NIPDTVGVMH
     PFKFYDLISK IVKVTGDKIV SVHCHNDFGL ATANSIAGVM AGARQVHVTV NGIGERAGNA
     SLEEVVMSLK KLLGYDVGVR TYLLYEVSRY VAELTGVPVP YFKAIVGENA FGHEAGIHVH
     GVIENPMTYE PISPEEVGNF RRIALGKHSG IHGLKRLLEE QGIFLDDTQL REVLKEIKSL
     AEAGNKVTSA DAKAIAIKVI NKKITA