ID LEU1_NEIMF Reviewed; 517 AA. AC A1KTV6; DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot. DT 06-FEB-2007, sequence version 1. DT 27-MAR-2024, entry version 93. 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=NMC1034; OS Neisseria meningitidis serogroup C / serotype 2a (strain ATCC 700532 / DSM OS 15464 / FAM18). OC Bacteria; Pseudomonadota; Betaproteobacteria; Neisseriales; Neisseriaceae; OC Neisseria. OX NCBI_TaxID=272831; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700532 / DSM 15464 / FAM18; RX PubMed=17305430; DOI=10.1371/journal.pgen.0030023; RA Bentley S.D., Vernikos G.S., Snyder L.A.S., Churcher C., Arrowsmith C., RA Chillingworth T., Cronin A., Davis P.H., Holroyd N.E., Jagels K., RA Maddison M., Moule S., Rabbinowitsch E., Sharp S., Unwin L., Whitehead S., RA Quail M.A., Achtman M., Barrell B.G., Saunders N.J., Parkhill J.; RT "Meningococcal genetic variation mechanisms viewed through comparative RT analysis of serogroup C strain FAM18."; RL PLoS Genet. 3:230-240(2007). 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; AM421808; CAM10296.1; -; Genomic_DNA. DR AlphaFoldDB; A1KTV6; -. DR SMR; A1KTV6; -. DR KEGG; nmc:NMC1034; -. DR HOGENOM; CLU_022158_0_1_4; -. DR UniPathway; UPA00048; UER00070. DR Proteomes; UP000002286; 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..517 FT /note="2-isopropylmalate synthase" FT /id="PRO_1000149226" FT DOMAIN 7..269 FT /note="Pyruvate carboxyltransferase" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT REGION 395..517 FT /note="Regulatory domain" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 16 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 204 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 206 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" FT BINDING 240 FT /ligand="Mn(2+)" FT /ligand_id="ChEBI:CHEBI:29035" FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025" SQ SEQUENCE 517 AA; 55425 MW; 97E99448542990D6 CRC64; MTQANRVIIF DTTLRDGEQS PGAAMTKEEK IRVARQLEKL GVDIIEAGFA AASPGDFEAV NAIAKTITKS TVCSLSRAIE RDIRQAGEAV APAPKKRIHT FIATSPIHME YKLKMKPKQV IEAAVKAVKI AREYTDDVEF SCEDALRSEI DFLAEICGAV IEAGATTINI PDTVGYSIPY KTEEFFRELI VKTPNGGKVV WSAHCHNDLG LAVANSLAAL KGGARQVECT VNGLGERAGN ASVEEIVMAL KVRHDLFGLE TGIDTTQIVP SSKLVSTITG YPVQPNKAIV GANAFSHESG IHQDGVLKHR ETYEIMSAES VGWATNRLSL GKLSGRNAFK TKLADLGIEL ESEEALNAAF ARFKELADKK REIFDEDLHA LVSDEMGSMN AESYKFISQK ISTETGEEPR ADIVFSIKGE EKRASATGSG PVDAIFKAIE SVAQSGATLQ IYSVNAVTQG TESQGETSVR LARGNRVVNG QGADTDVLVA TAKAYLSALS KLEFSAAKPK AQGSGTI //