LEU1_SALTY
ID LEU1_SALTY Reviewed; 523 AA.
AC P15875; P74845;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=2-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025, ECO:0000305};
DE EC=2.3.3.13 {ECO:0000255|HAMAP-Rule:MF_01025, ECO:0000269|PubMed:4976555, ECO:0000269|PubMed:6195343};
DE AltName: Full=Alpha-IPM synthase {ECO:0000255|HAMAP-Rule:MF_01025, ECO:0000303|PubMed:6195343};
DE AltName: Full=Alpha-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025, ECO:0000303|PubMed:4976555};
GN Name=leuA {ECO:0000303|PubMed:6195343}; OrderedLocusNames=STM0113;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=LT2;
RX PubMed=2181403; DOI=10.1093/nar/18.5.1290;
RA Ricca E., Calvo J.M.;
RT "The nucleotide sequence of leuA from Salmonella typhimurium.";
RL Nucleic Acids Res. 18:1290-1290(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
RC STRAIN=LT2;
RX PubMed=388423; DOI=10.1073/pnas.76.10.4941;
RA Gemmill R.M., Wessler S.R., Keller E.B., Calvo J.M.;
RT "Leu operon of Salmonella typhimurium is controlled by an attenuation
RT mechanism.";
RL Proc. Natl. Acad. Sci. U.S.A. 76:4941-4945(1979).
RN [4]
RP PROTEIN SEQUENCE OF 2-12, FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=LT2;
RX PubMed=6195343; DOI=10.1016/s0022-2836(83)80226-5;
RA Gemmill R.M., Jones J.W., Haughn G.W., Calvo J.M.;
RT "Transcription initiation sites of the leucine operons of Salmonella
RT typhimurium and Escherichia coli.";
RL J. Mol. Biol. 170:39-59(1983).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL
RP PROPERTIES.
RC STRAIN=CV-19;
RX PubMed=4976555; DOI=10.1016/s0021-9258(18)97789-6;
RA Kohlhaw G., Leary T.R., Umbarger H.E.;
RT "Alpha-isopropylmalate synthase from Salmonella typhimurium. Purification
RT and properties.";
RL J. Biol. Chem. 244:2218-2225(1969).
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:0000255|HAMAP-
CC Rule:MF_01025, ECO:0000269|PubMed:4976555, ECO:0000269|PubMed:6195343}.
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:0000255|HAMAP-Rule:MF_01025,
CC ECO:0000269|PubMed:4976555, ECO:0000269|PubMed:6195343};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA, mercuric salts and by leucine.
CC Inhibition by leucine is non-competitive with respect to 3-methyl-2-
CC oxobutanoate and competitive with respect to acetyl-CoA, and is more
CC sensitive at pH 6.5 than pH 8.5. {ECO:0000269|PubMed:4976555}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.06 mM for 3-methyl-2-oxobutanoate {ECO:0000269|PubMed:4976555};
CC KM=1.1 mM for 2-oxobutanoate {ECO:0000269|PubMed:4976555};
CC KM=10 mM for pyruvate {ECO:0000269|PubMed:4976555};
CC KM=0.2 mM for acetyl-CoA {ECO:0000269|PubMed:4976555};
CC pH dependence:
CC Optimum pH is 8.5. {ECO:0000269|PubMed:4976555};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000255|HAMAP-
CC Rule:MF_01025}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_01025}.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. LeuA type 1 subfamily. {ECO:0000255|HAMAP-Rule:MF_01025,
CC ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA35931.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; X51583; CAA35931.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AE006468; AAL19077.1; -; Genomic_DNA.
DR EMBL; X00059; CAA24935.1; -; Genomic_DNA.
DR RefSeq; NP_459118.1; NC_003197.2.
DR RefSeq; WP_000082819.1; NC_003197.2.
DR AlphaFoldDB; P15875; -.
DR SMR; P15875; -.
DR STRING; 99287.STM0113; -.
DR PaxDb; P15875; -.
DR EnsemblBacteria; AAL19077; AAL19077; STM0113.
DR GeneID; 1251631; -.
DR KEGG; stm:STM0113; -.
DR PATRIC; fig|99287.12.peg.119; -.
DR HOGENOM; CLU_022158_0_1_6; -.
DR OMA; NTMRMLV; -.
DR PhylomeDB; P15875; -.
DR BioCyc; SENT99287:STM0113-MON; -.
DR UniPathway; UPA00048; UER00070.
DR Proteomes; UP000001014; Chromosome.
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 Gene3D; 3.30.160.270; -; 1.
DR HAMAP; MF_01025; LeuA_type1; 1.
DR InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR InterPro; IPR005671; LeuA_bact_synth.
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; TIGR00973; leuA_bact; 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 Direct protein sequencing; Leucine biosynthesis; Reference proteome;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:6195343"
FT CHAIN 2..523
FT /note="2-isopropylmalate synthase"
FT /id="PRO_0000140375"
FT DOMAIN 5..267
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT CONFLICT 113
FT /note="S -> R (in Ref. 1; CAA35931)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 523 AA; 57431 MW; 0F5271BC488E7671 CRC64;
MSQQVIIFDT TLRDGEQALQ ASLSAKEKLQ IALALERMGV DVMEVGFPVS SPGDFESVQT
IARTIKNSRV CALARCVEKD IDVAAQALKV ADAFRIHTFI ATSPMHIATK LRSTLDEVIE
RAVYMVKRAR NYTDDVEFSC EDAGRTPVDD LARVVEAAIN AGARTINIPD TVGYTMPFEF
AGIISGLYER VPNIDKAIIS VHTHDDLGIA VGNSLAAVHA GARQVEGAMN GIGERAGNCA
LEEVIMAIKV RKDIMNVHTN INHHEIWRTS QTVSQICNMP IPANKAIVGS GAFAHSSGIH
QDGVLKNREN YEIMTPESIG LNQIQLNLTS RSGRAAVKHR MEEMGYKDTD YNMDHLYDAF
LKLADKKGQV FDYDLEALAF INKQQEEPEH FRLDYFSVQS GSSDIATASV KLACGEEIKA
EAANGNGPVD AIYQAINRIT GYDVELVKYD LNAKGQGKDA LGQVDIVVNH HGRRFHGVGL
ATDIVESSAK AMVHVLNNIW RAAEVEKELQ RKAQNKENNK ETV
