ID LEU1_GEOSW Reviewed; 515 AA. AC C5D5M0; DT 22-SEP-2009, integrated into UniProtKB/Swiss-Prot. DT 28-JUL-2009, sequence version 1. DT 27-MAR-2024, entry version 76. DE RecName: Full=2-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025}; DE EC=2.3.3.13 {ECO:0000255|HAMAP-Rule:MF_01025}; DE AltName: Full=Alpha-IPM synthase {ECO:0000255|HAMAP-Rule:MF_01025}; DE AltName: Full=Alpha-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_01025}; GN Name=leuA {ECO:0000255|HAMAP-Rule:MF_01025}; GN OrderedLocusNames=GWCH70_2593; OS Geobacillus sp. (strain WCH70). OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Geobacillus. OX NCBI_TaxID=471223; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=WCH70; RG US DOE Joint Genome Institute; RA Lucas S., Copeland A., Lapidus A., Glavina del Rio T., Dalin E., Tice H., RA Bruce D., Goodwin L., Pitluck S., Chertkov O., Brettin T., Detter J.C., RA Han C., Larimer F., Land M., Hauser L., Kyrpides N., Mikhailova N., RA Brumm P., Mead D.A., Richardson P.; RT "Complete sequence of chromosome of Geopacillus sp. WCH70."; RL Submitted (JUN-2009) 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:0000255|HAMAP- CC Rule:MF_01025}. 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 -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000255|HAMAP- CC Rule:MF_01025}; 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: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01025}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; CP001638; ACS25288.1; -; Genomic_DNA. DR AlphaFoldDB; C5D5M0; -. DR SMR; C5D5M0; -. DR STRING; 471223.GWCH70_2593; -. DR KEGG; gwc:GWCH70_2593; -. DR eggNOG; COG0119; Bacteria. DR HOGENOM; CLU_022158_0_1_9; -. DR OrthoDB; 9804858at2; -. DR UniPathway; UPA00048; UER00070. 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:0030145; F:manganese ion binding; IEA:UniProtKB-UniRule. DR GO; GO:0009098; P:leucine biosynthetic process; IEA:UniProtKB-UniRule. DR CDD; cd07940; DRE_TIM_IPMS; 1. DR Gene3D; 1.10.238.260; -; 1. DR Gene3D; 3.30.160.270; -; 1. DR Gene3D; 3.20.20.70; Aldolase class I; 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 NCBIfam; TIGR00973; leuA_bact; 1. DR PANTHER; PTHR10277:SF9; 2-ISOPROPYLMALATE SYNTHASE 1, CHLOROPLASTIC-RELATED; 1. DR PANTHER; PTHR10277; HOMOCITRATE SYNTHASE-RELATED; 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 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; Cytoplasm; KW Leucine biosynthesis; Manganese; Metal-binding; Transferase. FT CHAIN 1..515 FT /note="2-isopropylmalate synthase" FT /id="PRO_1000213314" FT DOMAIN 4..266 FT /note="Pyruvate carboxyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT REGION 391..515 FT /note="Regulatory domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 13 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 201 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 203 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 237 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" SQ SEQUENCE 515 AA; 56758 MW; BD59459DE3FDC9BB CRC64; MRKINIFDTT LRDGEQSAGI NLNLQEKLEI ARQLERLGVD IIEAGFPASS KGDFQAVKQI AETIKTCSVT GLARSVQSDI DAAWEALKGG AEPRLHLFIA TSPIHMKYKL QMTPEQVIET AVESVKYAKR YFPIVQWSAE DACRSELPFL AKIITEVIKA GATVINIPDT VGYITPKEYG NIFTFLSNNV PNIEKVSLSA HCHDDLGMAV ANSLAAIEHG ATQIEGTING IGERAGNAAL EEIAVALYIR KDYYQAETRL NLQEIKRTSN LVSKLTGVVI PPNKAVIGKN AFAHESGIHQ DGVLKEKTTY EIISPELVGV QSNSMVLGKH SGRHALRNRV EELGYTLSDE EVNKLFVRFK ELADKKKDIT DDDLVALIFE EKFDHFKDFY QLSSLQVQYG TNQIPTAVVV LKDGQGNEIQ EAATGAGSVE ALYNTLERCF KTSVTLLDYR IESVSGGRDA LAQVFVKVRV NDIETSGRGT AQDVLEASAK AYINAVNRVF MIETMRAENQ KVAMQ //