ID R6K3C6_9BACE Unreviewed; 498 AA.
AC R6K3C6;
DT 24-JUL-2013, integrated into UniProtKB/TrEMBL.
DT 24-JUL-2013, sequence version 1.
DT 24-JAN-2024, entry version 49.
DE RecName: Full=2-isopropylmalate synthase {ECO:0000256|ARBA:ARBA00018198, ECO:0000256|HAMAP-Rule:MF_01025};
DE EC=2.3.3.13 {ECO:0000256|ARBA:ARBA00012973, ECO:0000256|HAMAP-Rule:MF_01025};
DE AltName: Full=Alpha-IPM synthase {ECO:0000256|HAMAP-Rule:MF_01025};
DE AltName: Full=Alpha-isopropylmalate synthase {ECO:0000256|HAMAP-Rule:MF_01025};
GN Name=leuA {ECO:0000256|HAMAP-Rule:MF_01025};
GN ORFNames=BN506_00073 {ECO:0000313|EMBL:CDB69528.1};
OS Bacteroides cellulosilyticus CAG:158.
OC Bacteria; Bacteroidota; Bacteroidia; Bacteroidales; Bacteroidaceae;
OC Bacteroides.
OX NCBI_TaxID=1263038 {ECO:0000313|EMBL:CDB69528.1, ECO:0000313|Proteomes:UP000018191};
RN [1] {ECO:0000313|EMBL:CDB69528.1, ECO:0000313|Proteomes:UP000018191}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MGS:158 {ECO:0000313|Proteomes:UP000018191};
RA Nielsen H.B., Almeida M., Juncker A.S., Rasmussen S., Li J., Sunagawa S.,
RA Plichta D., Gautier L., Le Chatelier E., Peletier E., Bonde I., Nielsen T.,
RA Manichanh C., Arumugam M., Batto J., Santos M.B.Q.D., Blom N., Borruel N.,
RA Burgdorf K.S., Boumezbeur F., Casellas F., Dore J., Guarner F., Hansen T.,
RA Hildebrand F., Kaas R.S., Kennedy S., Kristiansen K., Kultima J.R.,
RA Leonard P., Levenez F., Lund O., Moumen B., Le Paslier D., Pons N.,
RA Pedersen O., Prifti E., Qin J., Raes J., Tap J., Tims S., Ussery D.W.,
RA Yamada T., MetaHit consortium, Renault P., Sicheritz-Ponten T., Bork P.,
RA Wang J., Brunak S., Ehrlich S.D.;
RT "Dependencies among metagenomic species, viruses, plasmids and units of
RT genetic variation.";
RL Submitted (NOV-2012) 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_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:0000256|HAMAP-Rule:MF_01025};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000256|HAMAP-Rule:MF_01025};
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_01025}.
CC -!- SUBUNIT: Homodimer. {ECO:0000256|HAMAP-Rule:MF_01025}.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. LeuA type 1 subfamily. {ECO:0000256|ARBA:ARBA00009396,
CC ECO:0000256|HAMAP-Rule:MF_01025}.
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:CDB69528.1}.
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DR EMBL; CBEB010000002; CDB69528.1; -; Genomic_DNA.
DR AlphaFoldDB; R6K3C6; -.
DR UniPathway; UPA00048; UER00070.
DR Proteomes; UP000018191; Unassembled WGS sequence.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-UniRule.
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; 3.30.160.740; -; 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 {ECO:0000256|ARBA:ARBA00022605, ECO:0000256|HAMAP-
KW Rule:MF_01025};
KW Branched-chain amino acid biosynthesis {ECO:0000256|ARBA:ARBA00023304,
KW ECO:0000256|HAMAP-Rule:MF_01025};
KW Cytoplasm {ECO:0000256|HAMAP-Rule:MF_01025};
KW Leucine biosynthesis {ECO:0000256|ARBA:ARBA00022430, ECO:0000256|HAMAP-
KW Rule:MF_01025};
KW Manganese {ECO:0000256|ARBA:ARBA00023211, ECO:0000256|HAMAP-Rule:MF_01025};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723, ECO:0000256|HAMAP-
KW Rule:MF_01025}; Reference proteome {ECO:0000313|Proteomes:UP000018191};
KW Transferase {ECO:0000256|ARBA:ARBA00022679, ECO:0000256|HAMAP-
KW Rule:MF_01025}.
FT DOMAIN 5..266
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000259|PROSITE:PS50991"
FT REGION 389..498
FT /note="Regulatory domain"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01025"
FT BINDING 14
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01025"
FT BINDING 202
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01025"
FT BINDING 204
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01025"
FT BINDING 238
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000256|HAMAP-Rule:MF_01025"
SQ SEQUENCE 498 AA; 54529 MW; 9A6BA4C4BAC03DEE CRC64;
MSDKLFIFDT TLRDGEQVPG CQLNTVEKIQ VAKALELLGV DVIEAGFPIS SPGDFNSVIE
ISKAVTWPTI CALTRAVQKD IDVAADALKF AKHKRIHTGI GTSDSHIKYK FNSNREEIIE
RAVAAVKYAR RYVDDVEFYA EDAGRTDNEY LARVVEAVIK AGATVVNIPD TTGYCLPDEY
GAKIKYLMEH VSGIEKAILS THCHNDLGMA TANTMAGVLN GARQVEVTIN GIGERAGNTS
LEEVAMIIKC HKDIEIETNI NTQKIYPTSR MVSSLMNMPV QPNKAIVGRN AFAHSSGIHQ
DGVLKNVQTY EIIDPHDVGI DDNSIVLTAR SGRAALKNRL QVLGVELEQE QLDKVYEAFL
KLADKKKDIN DDDILVLAGA DRTQNHRVKL EYLQVTSGVG VRSVASLGLN ISGEKFEAAA
SGNGPVDAAI KALKKIIDRH MTLKEFTIQA ISKGSDDMGK VHMQVEYDNH IYYGFGANTD
IIAASVEAYI DCINKFKS
//