ID LEU1_BACCZ Reviewed; 506 AA. AC Q63DX8; DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot. DT 25-OCT-2004, sequence version 1. DT 27-MAR-2024, entry version 114. 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=BCE33L1285; OS Bacillus cereus (strain ZK / E33L). OC Bacteria; Bacillota; Bacilli; Bacillales; Bacillaceae; Bacillus; OC Bacillus cereus group. OX NCBI_TaxID=288681; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ZK / E33L; RX PubMed=16621833; DOI=10.1128/jb.188.9.3382-3390.2006; RA Han C.S., Xie G., Challacombe J.F., Altherr M.R., Bhotika S.S., Bruce D., RA Campbell C.S., Campbell M.L., Chen J., Chertkov O., Cleland C., RA Dimitrijevic M., Doggett N.A., Fawcett J.J., Glavina T., Goodwin L.A., RA Hill K.K., Hitchcock P., Jackson P.J., Keim P., Kewalramani A.R., RA Longmire J., Lucas S., Malfatti S., McMurry K., Meincke L.J., Misra M., RA Moseman B.L., Mundt M., Munk A.C., Okinaka R.T., Parson-Quintana B., RA Reilly L.P., Richardson P., Robinson D.L., Rubin E., Saunders E., Tapia R., RA Tesmer J.G., Thayer N., Thompson L.S., Tice H., Ticknor L.O., Wills P.L., RA Brettin T.S., Gilna P.; RT "Pathogenomic sequence analysis of Bacillus cereus and Bacillus RT thuringiensis isolates closely related to Bacillus anthracis."; RL J. Bacteriol. 188:3382-3390(2006). 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; CP000001; AAU18963.1; -; Genomic_DNA. DR RefSeq; WP_000721813.1; NZ_CP009968.1. DR AlphaFoldDB; Q63DX8; -. DR SMR; Q63DX8; -. DR KEGG; bcz:BCE33L1285; -. DR PATRIC; fig|288681.22.peg.4269; -. DR UniPathway; UPA00048; UER00070. DR Proteomes; UP000002612; Chromosome. 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..506 FT /note="2-isopropylmalate synthase" FT /id="PRO_1000149134" FT DOMAIN 4..266 FT /note="Pyruvate carboxyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT REGION 390..506 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 506 AA; 55401 MW; 4AB125DDC8596189 CRC64; MKKILFMDTT LRDGEQSPGV NLNEQEKLQI ARQLERLGIH VMEAGFAAAS EGDFQSVKRI ANTIQNATVM SLARAKESDI RRAYEAVKGA VSPRLHVFLA TSDIHMKYKL CMSKEDVLDS IYRSVTLGKS LFPTVQFSAE DATRTARDFL AEAVEVAIRA GANVINIPDT VGYTNPEEYY SLFKYLQESV PSYEKAIFSC HCHDDLGMAV ANSLAAVEGG ALQVEGTING IGERAGNAAL EEVAVALHIR KDFYKAEPSM TLKEIKATST LVSRLTGMVV PKNKAIVGAN AFAHESGIHQ DGVLKEVTTY EIIEPALVGE SQNLFVLGKH SGRHAFTEKM KELGYEFTND ERDAVFEAFK KLADRKKEIT EEDLRALMLG EAAFAAQQYN ITQLQVHFVS NSTQCATVVL KDEEGNVFED AATGSGSIEA IYNAIQRILG LECELADYRI QSITQGQDAL AHVHVELKEG AHQVSGFGVA QDVLEASARA YVHAAGKLKS FIQLVK //