ID F3B735_9FIRM Unreviewed; 554 AA.
AC F3B735;
DT 28-JUN-2011, integrated into UniProtKB/TrEMBL.
DT 28-JUN-2011, sequence version 1.
DT 27-MAR-2024, entry version 61.
DE RecName: Full=2-isopropylmalate synthase {ECO:0000256|ARBA:ARBA00012973, ECO:0000256|HAMAP-Rule:MF_00572};
DE EC=2.3.3.13 {ECO:0000256|ARBA:ARBA00012973, ECO:0000256|HAMAP-Rule:MF_00572};
DE AltName: Full=Alpha-IPM synthase {ECO:0000256|HAMAP-Rule:MF_00572};
DE AltName: Full=Alpha-isopropylmalate synthase {ECO:0000256|HAMAP-Rule:MF_00572};
GN Name=leuA {ECO:0000256|HAMAP-Rule:MF_00572};
GN ORFNames=HMPREF0491_02844 {ECO:0000313|EMBL:EGG90113.1};
OS Lachnospiraceae oral taxon 107 str. F0167.
OC Bacteria; Bacillota; Clostridia; Eubacteriales; Lachnospiraceae.
OX NCBI_TaxID=575593 {ECO:0000313|EMBL:EGG90113.1, ECO:0000313|Proteomes:UP000003263};
RN [1] {ECO:0000313|EMBL:EGG90113.1, ECO:0000313|Proteomes:UP000003263}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=F0167 {ECO:0000313|EMBL:EGG90113.1,
RC ECO:0000313|Proteomes:UP000003263};
RG The Broad Institute Genome Sequencing Platform;
RG The Broad Institute Genome Sequencing Center for Infectious Disease;
RA Earl A., Ward D., Feldgarden M., Gevers D., Izard J., Baranova O.V.,
RA Blanton J.M., Tanner A.C., Dewhirst F.E., Young S.K., Zeng Q., Gargeya S.,
RA Fitzgerald M., Haas B., Abouelleil A., Alvarado L., Arachchi H.M.,
RA Berlin A., Brown A., Chapman S.B., Chen Z., Dunbar C., Freedman E.,
RA Gearin G., Gellesch M., Goldberg J., Griggs A., Gujja S., Heilman E.R.,
RA Heiman D., Howarth C., Larson L., Lui A., MacDonald P.J.P., Mehta T.,
RA Montmayeur A., Murphy C., Neiman D., Pearson M., Priest M., Roberts A.,
RA Saif S., Shea T., Shenoy N., Sisk P., Stolte C., Sykes S., White J.,
RA Yandava C., Wortman J., Nusbaum C., Birren B.;
RT "The Genome Sequence of Lachnospiraceae bacterium oral taxon 107 strain
RT F0167.";
RL Submitted (MAR-2011) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA
CC with 3-methyl-2-oxobutanoate (2-ketoisovalerate) to form 3-carboxy-3-
CC hydroxy-4-methylpentanoate (2-isopropylmalate). {ECO:0000256|HAMAP-
CC Rule:MF_00572}.
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:0000256|ARBA:ARBA00000064, ECO:0000256|HAMAP-
CC Rule:MF_00572};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_00572};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 1/4. {ECO:0000256|ARBA:ARBA00004689,
CC ECO:0000256|HAMAP-Rule:MF_00572}.
CC -!- SUBUNIT: Homodimer. {ECO:0000256|HAMAP-Rule:MF_00572}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00572}.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. LeuA type 2 subfamily. {ECO:0000256|ARBA:ARBA00009767,
CC ECO:0000256|HAMAP-Rule:MF_00572}.
CC -!- CAUTION: The sequence shown here is derived from an EMBL/GenBank/DDBJ
CC whole genome shotgun (WGS) entry which is preliminary data.
CC {ECO:0000313|EMBL:EGG90113.1}.
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DR EMBL; ADDS01000054; EGG90113.1; -; Genomic_DNA.
DR AlphaFoldDB; F3B735; -.
DR STRING; 575593.HMPREF0491_02844; -.
DR eggNOG; COG0119; Bacteria.
DR HOGENOM; CLU_004588_3_0_9; -.
DR OrthoDB; 9804858at2; -.
DR UniPathway; UPA00048; UER00070.
DR Proteomes; UP000003263; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0003852; F:2-isopropylmalate synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0003985; F:acetyl-CoA C-acetyltransferase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProtKB-UniRule.
DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule.
DR CDD; cd07942; DRE_TIM_LeuA; 1.
DR Gene3D; 3.30.160.270; -; 1.
DR Gene3D; 3.20.20.70; Aldolase class I; 1.
DR HAMAP; MF_00572; LeuA_type2; 1.
DR InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005668; IPM_Synthase.
DR InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR InterPro; IPR039371; LeuA_N_DRE-TIM.
DR InterPro; IPR000891; PYR_CT.
DR NCBIfam; TIGR00970; leuA_yeast; 1.
DR PANTHER; PTHR46911; -; 1.
DR PANTHER; PTHR46911:SF1; 2-ISOPROPYLMALATE SYNTHASE; 1.
DR Pfam; PF00682; HMGL-like; 1.
DR Pfam; PF08502; LeuA_dimer; 1.
DR SMART; SM00917; LeuA_dimer; 1.
DR SUPFAM; SSF110921; 2-isopropylmalate synthase LeuA, allosteric (dimerisation) domain; 1.
DR SUPFAM; SSF51569; Aldolase; 1.
DR SUPFAM; SSF89000; post-HMGL domain-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 3: Inferred from homology;
KW Amino-acid biosynthesis {ECO:0000256|HAMAP-Rule:MF_00572};
KW Branched-chain amino acid biosynthesis {ECO:0000256|ARBA:ARBA00023304,
KW ECO:0000256|HAMAP-Rule:MF_00572};
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_00572};
KW Leucine biosynthesis {ECO:0000256|HAMAP-Rule:MF_00572};
KW Magnesium {ECO:0000256|HAMAP-Rule:MF_00572};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_00572}; Reference proteome {ECO:0000313|Proteomes:UP000003263};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|HAMAP-
KW Rule:MF_00572}.
FT DOMAIN 29..302
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000259|PROSITE:PS50991"
FT REGION 435..554
FT /note="Regulatory domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00572"
FT BINDING 38
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00572"
FT BINDING 241
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00572"
FT BINDING 243
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00572"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_00572"
SQ SEQUENCE 554 AA; 62607 MW; 5A4E034E324412C0 CRC64;
MYHIERYKRN PVVDFKERTW PDKQIEKAPI WCSSDLRDGN QALVEPMVVE EKIEMFNLLV
KLGFKEIEIG FPAASQIEFD FLRQLVDRKL IPDDVVVQVL CQCREHLIKR SFEAIQGIKK
CIMHIYNSTD TLQRDVVYAL DREGIKNIAL EGVDLVKKYM KDHDGEIILE YSPESFMGTE
LDFALDVCDA VVDAWGATKD KKIIINLPNT VEMTTPNVFA DRIEWMSIHL KNREAIILST
HPHNDRGTGT AVAELALLAG ADRMEGTLFG NGERTGNVDI LNIAYNMFSQ GINPNLNISN
IKEIIDVYER TTKMSIDPRH PYAGKLVFTA FSGSHQDAIN KGVQAMRQRN NPYWEVPYLP
IDPADIGREY EPVVRINSQS GKGGVAFVMD TFYGFKLPKS MHKEFADIIQ KISETQGEVS
PEEIYKEFEK NYIEKKEPLH FGKCVITDAD EDGDFSTFVK VTYTLNGEKR VFESTGNGPI
DAVKRGLENV IGKEIKVLDY NEHALTSGSN AKAASYIHML DVESGKTTYG VGISGNITKS
SIRGLFSAIN RLFY
//
