ILVX_MYCTU
ID ILVX_MYCTU Reviewed; 515 AA.
AC O53554; L0TFM4;
DT 10-AUG-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Putative acetolactate synthase large subunit IlvX;
DE Short=ALS;
DE EC=2.2.1.6;
DE AltName: Full=Acetohydroxy-acid synthase large subunit;
DE Short=AHAS;
GN Name=ilvX; OrderedLocusNames=Rv3509c;
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 [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 [2]
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 [3]
RP INDUCTION.
RX PubMed=20884690; DOI=10.1099/mic.0.041343-0;
RA Singh V., Chandra D., Srivastava B.S., Srivastava R.;
RT "Biochemical and transcription analysis of acetohydroxyacid synthase
RT isoforms in Mycobacterium tuberculosis identifies these enzymes as
RT potential targets for drug development.";
RL Microbiology 157:29-37(2011).
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 conversion of 2 pyruvate molecules into
CC acetolactate in the first common step of the biosynthetic pathway of
CC the branched-amino acids such as leucine, isoleucine, and valine.
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + 2 pyruvate = (2S)-2-acetolactate + CO2;
CC Xref=Rhea:RHEA:25249, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:58476; EC=2.2.1.6;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000250};
CC -!- COFACTOR:
CC Name=thiamine diphosphate; Xref=ChEBI:CHEBI:58937;
CC Evidence={ECO:0000250};
CC Note=Binds 1 thiamine pyrophosphate per subunit. {ECO:0000250};
CC -!- PATHWAY: Amino-acid biosynthesis; L-isoleucine biosynthesis; L-
CC isoleucine from 2-oxobutanoate: step 1/4.
CC -!- PATHWAY: Amino-acid biosynthesis; L-valine biosynthesis; L-valine from
CC pyruvate: step 1/4.
CC -!- SUBUNIT: Heterodimer of large catalytic subunit and small regulatory
CC subunit. {ECO:0000250}.
CC -!- INDUCTION: The expression is high during the mid-exponential phase and
CC low during the stationary phase. {ECO:0000269|PubMed:20884690}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
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DR EMBL; AL123456; CCP46331.1; -; Genomic_DNA.
DR PIR; G70806; G70806.
DR RefSeq; NP_218026.1; NC_000962.3.
DR RefSeq; WP_003900872.1; NZ_NVQJ01000085.1.
DR AlphaFoldDB; O53554; -.
DR SMR; O53554; -.
DR STRING; 83332.Rv3509c; -.
DR PaxDb; O53554; -.
DR DNASU; 888267; -.
DR GeneID; 888267; -.
DR KEGG; mtu:Rv3509c; -.
DR TubercuList; Rv3509c; -.
DR eggNOG; COG0028; Bacteria.
DR InParanoid; O53554; -.
DR OMA; DFRHEEP; -.
DR PhylomeDB; O53554; -.
DR BRENDA; 2.2.1.6; 3445.
DR UniPathway; UPA00047; UER00055.
DR UniPathway; UPA00049; UER00059.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005576; C:extracellular region; HDA:MTBBASE.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0005886; C:plasma membrane; HDA:MTBBASE.
DR GO; GO:0003984; F:acetolactate synthase activity; IBA:GO_Central.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IEA:UniProt.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IEA:InterPro.
DR GO; GO:0009097; P:isoleucine biosynthetic process; ISS:UniProtKB.
DR GO; GO:0009099; P:valine biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR045229; TPP_enz.
DR InterPro; IPR011766; TPP_enzyme-bd_C.
DR PANTHER; PTHR18968; PTHR18968; 2.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis; FAD;
KW Flavoprotein; Magnesium; Metal-binding; Reference proteome;
KW Thiamine pyrophosphate; Transferase.
FT CHAIN 1..515
FT /note="Putative acetolactate synthase large subunit IlvX"
FT /id="PRO_0000396953"
FT REGION 357..436
FT /note="Thiamine pyrophosphate binding"
FT /evidence="ECO:0000250"
FT BINDING 48
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 249..269
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 283..302
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 407
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 434
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
SQ SEQUENCE 515 AA; 52072 MW; 2E414C8CE49BADD6 CRC64;
MNGAQALINT LVDGGVDVCF ANPGTSEMHF VAALDAVPRM RGMLTLFEGV ATGAADGYAR
IAGRPAAVLL HLGPGLGNGL ANLHNARRAR VPMVVVVGDH ATYHKKYDAP LESDIDAVAG
TVSGWVRRTE AAADVGADAE AAIAASRSGS QIATLILPAD VCWSDGAHAA AGVPAQAAAA
PVDVGPVAGV LRSGEPAMML IGGDATRGPG LTAAARIVQA TGARWLCETF PTCLERGAGI
PAVERLAYFA EGAAAQLDGV KHLVLAGARS PVSFFAYPGM PSDLVPAGCE VHVLAEPGGA
ADALAALADE VAPGTVAPVA GASRPQLPTG DLTSVSAADV VGALLPERAI VVDESNTCGV
LLPQATAGAP AHDWLTLTGG AIGYGIPAAV GAAVAAPDRP VLCLESDGSA MYTISGLWSQ
ARENLDVTTV IYNNGAYDIL RIELQRVGAG SDPGPKALDL LDISRPTMDF VKIAEGMGVP
ARRVTTCEEF ADALRAAFAE PGPHLIDVVV PSLVG
