ID LEU1_NEIG1 Reviewed; 597 AA.
AC Q5F8D4;
DT 28-JUL-2009, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2023, sequence version 2.
DT 27-MAR-2024, entry version 109.
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}; OrderedLocusNames=NGO0848;
OS Neisseria gonorrhoeae (strain ATCC 700825 / FA 1090).
OC Bacteria; Pseudomonadota; Betaproteobacteria; Neisseriales; Neisseriaceae;
OC Neisseria.
OX NCBI_TaxID=242231;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 700825 / FA 1090;
RA Lewis L.A., Gillaspy A.F., McLaughlin R.E., Gipson M., Ducey T.F.,
RA Ownbey T., Hartman K., Nydick C., Carson M.B., Vaughn J., Thomson C.,
RA Song L., Lin S., Yuan X., Najar F., Zhan M., Ren Q., Zhu H., Qi S.,
RA Kenton S.M., Lai H., White J.D., Clifton S., Roe B.A., Dyer D.W.;
RT "The complete genome sequence of Neisseria gonorrhoeae.";
RL Submitted (MAR-2003) 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;
CC Evidence={ECO:0000255|HAMAP-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 -!- CAUTION: It is uncertain whether Met-1 or Met-81 is the initiator. Has
CC been predicted to be much longer than most orthologs, this longer
CC version can be predicted for many Neisseria species. {ECO:0000305}.
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DR EMBL; AE004969; AAW89553.2; -; Genomic_DNA.
DR RefSeq; WP_010358189.1; NC_002946.2.
DR AlphaFoldDB; Q5F8D4; -.
DR SMR; Q5F8D4; -.
DR STRING; 242231.NGO_0848; -.
DR KEGG; ngo:NGO_0848; -.
DR PATRIC; fig|242231.10.peg.1002; -.
DR HOGENOM; CLU_022158_0_1_4; -.
DR UniPathway; UPA00048; UER00070.
DR Proteomes; UP000000535; 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; Reference proteome;
KW Transferase.
FT CHAIN 1..597
FT /note="2-isopropylmalate synthase"
FT /id="PRO_1000149225"
FT DOMAIN 87..349
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
FT REGION 1..80
FT /note="Unknown"
FT /evidence="ECO:0000305"
FT REGION 87..349
FT /note="2-isopropylmalate synthase"
FT /evidence="ECO:0000305"
FT REGION 475..597
FT /note="Regulatory domain"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
FT BINDING 96
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
FT BINDING 284
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
FT BINDING 286
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
FT BINDING 320
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01025"
SQ SEQUENCE 597 AA; 64228 MW; 0DA1CCC3FB69D381 CRC64;
MQLDIDRLVA YFGGVNALAE ALKRHDPENA ATTAAIYKWR TRGSLPLAQL QKLTALAESQ
GRPLDLNAFL QKNESLERTE MTQANRVIIF DTTLRDGEQS PGAAMTKEEK IRVARQLEKL
GADIIEAGFA AASPGDFEAV NAIAKTITKS TVCSLSRAIE RDIRQAGKAV APAPKKRIHT
FIATSPIHME YKLKMKPKQV IEAAVKAVKI AREYTDDVEF SCEDALRSQI DFLAEICGAV
IEAGATTINI PDTVGYSIPY KTEEFFRELI AKTPNGGKVV WSAHCHNDLG LAVANSLAAL
KGGARQVECT VNGLGERAGN ASVEEIVMAL KVRHDLFGLE TGIDTTQIVP SSKLVSTITG
YPVQPNKAIV GANAFSHESG IHQDGVLKHR ETYEIMSAES VGWSANRLSL GKLSGRNAFK
TKLADLGIEL ESEEALNAAF ARFKELADKK REIFDEDLHA LVSDEMGNMN AESYKFISQK
ISTETGEEPR ADIVFGIKGE EKRASATGSG PVDAIFKAIE SVAQSGATLQ IYSVNAVTQG
TESQGETSVR LARGNRVVNG QGADTDILAA TAKAYLSALS KLEFSAAKPK AQGSGTI
//
