LEU1_MYCTU
ID LEU1_MYCTU Reviewed; 644 AA.
AC P9WQB3; L0TGA3; O69677; P96420;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 25-MAY-2022, entry version 39.
DE RecName: Full=2-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_00572};
DE EC=2.3.3.13 {ECO:0000255|HAMAP-Rule:MF_00572};
DE AltName: Full=Alpha-IPM synthase {ECO:0000255|HAMAP-Rule:MF_00572};
DE AltName: Full=Alpha-isopropylmalate synthase {ECO:0000255|HAMAP-Rule:MF_00572};
GN Name=leuA {ECO:0000255|HAMAP-Rule:MF_00572}; OrderedLocusNames=Rv3710;
GN ORFNames=MTV025.058;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=11914056; DOI=10.1054/tube.2001.0314;
RA Chanchaem W., Palittapongarnpim P.;
RT "A variable number of tandem repeats result in polymorphic alpha-
RT isopropylmalate synthase in Mycobacterium tuberculosis.";
RL Tuberculosis 82:1-6(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
CC -!- FUNCTION: Catalyzes the condensation of the acetyl group of acetyl-CoA
CC with 3-methyl-2-oxobutanoate (2-oxoisovalerate) to form 3-carboxy-3-
CC hydroxy-4-methylpentanoate (2-isopropylmalate). {ECO:0000255|HAMAP-
CC Rule:MF_00572}.
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_00572};
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_00572}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000255|HAMAP-Rule:MF_00572}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the alpha-IPM synthase/homocitrate synthase
CC family. LeuA type 2 subfamily. {ECO:0000255|HAMAP-Rule:MF_00572}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB48096.1; Type=Frameshift; Evidence={ECO:0000305};
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; U88526; AAB48096.1; ALT_FRAME; Genomic_DNA.
DR EMBL; AL123456; CCP46536.1; -; Genomic_DNA.
DR PIR; G70794; G70794.
DR RefSeq; NP_218227.3; NC_000962.3.
DR RefSeq; WP_003902547.1; NZ_NVQJ01000009.1.
DR PDB; 1SR9; X-ray; 2.00 A; A/B=1-644.
DR PDB; 3FIG; X-ray; 2.30 A; A/B=3-644.
DR PDB; 3HPS; X-ray; 1.80 A; A/B=1-644.
DR PDB; 3HPX; X-ray; 2.03 A; A/B=1-425.
DR PDB; 3HPZ; X-ray; 2.20 A; A/B=1-644.
DR PDB; 3HQ1; X-ray; 1.70 A; A/B=1-644.
DR PDB; 3U6W; X-ray; 2.21 A; A/B=1-425.
DR PDBsum; 1SR9; -.
DR PDBsum; 3FIG; -.
DR PDBsum; 3HPS; -.
DR PDBsum; 3HPX; -.
DR PDBsum; 3HPZ; -.
DR PDBsum; 3HQ1; -.
DR PDBsum; 3U6W; -.
DR AlphaFoldDB; P9WQB3; -.
DR SMR; P9WQB3; -.
DR STRING; 83332.Rv3710; -.
DR DrugBank; DB04074; alpha-Ketoisovalerate.
DR PaxDb; P9WQB3; -.
DR DNASU; 885092; -.
DR GeneID; 885092; -.
DR KEGG; mtu:Rv3710; -.
DR TubercuList; Rv3710; -.
DR eggNOG; COG0119; Bacteria.
DR OMA; WPDKVID; -.
DR BRENDA; 2.3.3.13; 3445.
DR UniPathway; UPA00048; UER00070.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003852; F:2-isopropylmalate synthase activity; IDA:MTBBASE.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030145; F:manganese ion binding; IDA:MTBBASE.
DR GO; GO:0030955; F:potassium ion binding; IDA:MTBBASE.
DR GO; GO:0008270; F:zinc ion binding; IDA:MTBBASE.
DR GO; GO:0009098; P:leucine biosynthetic process; IDA:MTBBASE.
DR CDD; cd07942; DRE_TIM_LeuA; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.30.160.270; -; 1.
DR HAMAP; MF_00572; LeuA_type2; 1.
DR InterPro; IPR013709; 2-isopropylmalate_synth_dimer.
DR InterPro; IPR002034; AIPM/Hcit_synth_CS.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR005668; IPM_Synthase.
DR InterPro; IPR036230; LeuA_allosteric_dom_sf.
DR InterPro; IPR039371; LeuA_N_DRE-TIM.
DR InterPro; IPR000891; PYR_CT.
DR Pfam; PF00682; HMGL-like; 1.
DR Pfam; PF08502; LeuA_dimer; 1.
DR SMART; SM00917; LeuA_dimer; 1.
DR SUPFAM; SSF110921; SSF110921; 1.
DR TIGRFAMs; TIGR00970; leuA_yeast; 1.
DR PROSITE; PS00815; AIPM_HOMOCIT_SYNTH_1; 1.
DR PROSITE; PS00816; AIPM_HOMOCIT_SYNTH_2; 1.
DR PROSITE; PS50991; PYR_CT; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Amino-acid biosynthesis;
KW Branched-chain amino acid biosynthesis; Leucine biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..644
FT /note="2-isopropylmalate synthase"
FT /id="PRO_0000140436"
FT DOMAIN 72..346
FT /note="Pyruvate carboxyltransferase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01151"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 577..614
FT /note="Insert"
FT REGION 581..612
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 628..633
FT /note="TTASLR -> NRPA (in Ref. 1; AAB48096)"
FT /evidence="ECO:0000305"
FT CONFLICT 642..644
FT /note="AAR -> RHARTALN (in Ref. 1; AAB48096)"
FT /evidence="ECO:0000305"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 49..52
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 63..65
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 73..76
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 78..82
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 92..105
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 108..113
FT /evidence="ECO:0007829|PDB:3HQ1"
FT TURN 115..117
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 119..130
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 148..158
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 162..171
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 174..179
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 185..205
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 208..218
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 220..222
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 225..239
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 243..245
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 247..255
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 260..273
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:3HPS"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 280..287
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 293..302
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 307..311
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 312..314
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 324..332
FT /evidence="ECO:0007829|PDB:3HQ1"
FT TURN 333..335
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 345..356
FT /evidence="ECO:0007829|PDB:3HQ1"
FT TURN 365..367
FT /evidence="ECO:0007829|PDB:3HQ1"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 377..396
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 401..403
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 415..418
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 437..445
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 451..463
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 477..488
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 493..503
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 512..520
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 523..533
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 534..543
FT /evidence="ECO:0007829|PDB:3HQ1"
FT TURN 544..546
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 548..562
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 567..576
FT /evidence="ECO:0007829|PDB:3HQ1"
FT STRAND 616..626
FT /evidence="ECO:0007829|PDB:3HQ1"
FT HELIX 627..642
FT /evidence="ECO:0007829|PDB:3HQ1"
SQ SEQUENCE 644 AA; 70114 MW; 881A9AAEA7F8FB71 CRC64;
MTTSESPDAY TESFGAHTIV KPAGPPRVGQ PSWNPQRASS MPVNRYRPFA EEVEPIRLRN
RTWPDRVIDR APLWCAVDLR DGNQALIDPM SPARKRRMFD LLVRMGYKEI EVGFPSASQT
DFDFVREIIE QGAIPDDVTI QVLTQCRPEL IERTFQACSG APRAIVHFYN STSILQRRVV
FRANRAEVQA IATDGARKCV EQAAKYPGTQ WRFEYSPESY TGTELEYAKQ VCDAVGEVIA
PTPERPIIFN LPATVEMTTP NVYADSIEWM SRNLANRESV ILSLHPHNDR GTAVAAAELG
FAAGADRIEG CLFGNGERTG NVCLVTLGLN LFSRGVDPQI DFSNIDEIRR TVEYCNQLPV
HERHPYGGDL VYTAFSGSHQ DAINKGLDAM KLDADAADCD VDDMLWQVPY LPIDPRDVGR
TYEAVIRVNS QSGKGGVAYI MKTDHGLSLP RRLQIEFSQV IQKIAEGTAG EGGEVSPKEM
WDAFAEEYLA PVRPLERIRQ HVDAADDDGG TTSITATVKI NGVETEISGS GNGPLAAFVH
ALADVGFDVA VLDYYEHAMS AGDDAQAAAY VEASVTIASP AQPGEAGRHA SDPVTIASPA
QPGEAGRHAS DPVTSKTVWG VGIAPSITTA SLRAVVSAVN RAAR
