ID   LEU12_LEPIN             Reviewed;         428 AA.
AC   Q8F8T4;
DT   22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2003, sequence version 1.
DT   25-MAY-2022, entry version 96.
DE   RecName: Full=2-isopropylmalate synthase 2 {ECO:0000305};
DE            EC=2.3.3.13 {ECO:0000269|PubMed:15292141};
DE   AltName: Full=Alpha-IPM synthase 2 {ECO:0000305};
DE   AltName: Full=Alpha-isopropylmalate synthase 2 {ECO:0000303|PubMed:15292141};
GN   Name=leuA2 {ECO:0000303|PubMed:15292141};
GN   OrderedLocusNames=LA_0469 {ECO:0000312|EMBL:AAN47668.1};
OS   Leptospira interrogans serogroup Icterohaemorrhagiae serovar Lai (strain
OS   56601).
OC   Bacteria; Spirochaetes; Leptospirales; Leptospiraceae; Leptospira.
OX   NCBI_TaxID=189518;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=56601;
RX   PubMed=12712204; DOI=10.1038/nature01597;
RA   Ren S.-X., Fu G., Jiang X.-G., Zeng R., Miao Y.-G., Xu H., Zhang Y.-X.,
RA   Xiong H., Lu G., Lu L.-F., Jiang H.-Q., Jia J., Tu Y.-F., Jiang J.-X.,
RA   Gu W.-Y., Zhang Y.-Q., Cai Z., Sheng H.-H., Yin H.-F., Zhang Y., Zhu G.-F.,
RA   Wan M., Huang H.-L., Qian Z., Wang S.-Y., Ma W., Yao Z.-J., Shen Y.,
RA   Qiang B.-Q., Xia Q.-C., Guo X.-K., Danchin A., Saint Girons I.,
RA   Somerville R.L., Wen Y.-M., Shi M.-H., Chen Z., Xu J.-G., Zhao G.-P.;
RT   "Unique physiological and pathogenic features of Leptospira interrogans
RT   revealed by whole-genome sequencing.";
RL   Nature 422:888-893(2003).
RN   [2]
RP   FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, PATHWAY, AND
RP   INDUCTION.
RC   STRAIN=56601;
RX   PubMed=15292141; DOI=10.1128/jb.186.16.5400-5409.2004;
RA   Xu H., Zhang Y., Guo X., Ren S., Staempfli A.A., Chiao J., Jiang W.,
RA   Zhao G.;
RT   "Isoleucine biosynthesis in Leptospira interrogans serotype lai strain
RT   56601 proceeds via a threonine-independent pathway.";
RL   J. Bacteriol. 186:5400-5409(2004).
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) (PubMed:15292141). Also
CC       has low citramalate synthase activity (PubMed:15292141).
CC       {ECO:0000269|PubMed:15292141}.
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:15292141};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21525;
CC         Evidence={ECO:0000269|PubMed:15292141};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.108 mM for 3-methyl-2-oxobutanoate
CC         {ECO:0000269|PubMed:15292141};
CC         KM=0.709 mM for pyruvate {ECO:0000269|PubMed:15292141};
CC   -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC       from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000269|PubMed:15292141}.
CC   -!- INDUCTION: Expression is significantly repressed by leucine and
CC       moderately repressed by isoleucine. {ECO:0000269|PubMed:15292141}.
CC   -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC       family. LeuA type 1 subfamily. {ECO:0000305}.
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DR   EMBL; AE010300; AAN47668.1; -; Genomic_DNA.
DR   RefSeq; NP_710650.1; NC_004342.2.
DR   RefSeq; WP_000806758.1; NC_004342.2.
DR   AlphaFoldDB; Q8F8T4; -.
DR   SMR; Q8F8T4; -.
DR   STRING; 189518.LA_0469; -.
DR   EnsemblBacteria; AAN47668; AAN47668; LA_0469.
DR   KEGG; lil:LA_0469; -.
DR   PATRIC; fig|189518.3.peg.477; -.
DR   HOGENOM; CLU_022158_0_2_12; -.
DR   OMA; WPDKVID; -.
DR   UniPathway; UPA00048; UER00070.
DR   Proteomes; UP000001408; Chromosome I.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0003852; F:2-isopropylmalate synthase activity; IBA:GO_Central.
DR   GO; GO:0009098; P:leucine biosynthetic process; IBA:GO_Central.
DR   Gene3D; 3.20.20.70; -; 1.
DR   InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR   InterPro; IPR013785; Aldolase_TIM.
DR   InterPro; IPR000891; PYR_CT.
DR   Pfam; PF00682; HMGL-like; 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..428
FT                   /note="2-isopropylmalate synthase 2"
FT                   /id="PRO_0000449423"
FT   DOMAIN          40..302
FT                   /note="Pyruvate carboxyltransferase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
SQ   SEQUENCE   428 AA;  47721 MW;  6B7543104A1D00CC CRC64;
     MKQDSQSENE SIVCDLSVSE DQRNVKFFSD LQTPIPKHLP FFMDVTLRDG NQALRRPWNL
     EQKETIFKQL LKLGVQGIEV GFASSNNQEF EACKYLSSIA PDNVVISSLS RAVEKEIEVS
     WKAIRFAPKP RIHIVYPVSA FTIQNVLKIS PEKVLDRISQ SVAYAKSLVG SKGEVQFSGE
     HFGDSLENLD FAAEAFQIAL NNGADVVNLP NTVERYRPWL FVSMVKAVAN LLPEDTRISI
     HTHNDLGMAT ATTVESYFAG AVQLETALNG LGERAGNTNT YEVAIALHNC GVEVPLNFST
     IYETSRLVSY LSEIPIYEKA PLIGEDVISH RSGIHQDGVA KTRHLQKGAY RAFDAALIGR
     PEGDRIEFTN QSGKSAVYCI LKDAGENITL EEAGRLQPIL KKISEDLGRR ELTLEEIRIE
     WNRLLRAI