ILVB1_MYCTU
ID ILVB1_MYCTU Reviewed; 618 AA.
AC P9WG41; L0TCV7; O53250; P0A622;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 41.
DE RecName: Full=Acetolactate synthase large subunit IlvB1;
DE Short=ALS;
DE EC=2.2.1.6;
DE AltName: Full=Acetohydroxy-acid synthase large subunit;
DE Short=AHAS;
GN Name=ilvB1; OrderedLocusNames=Rv3003c; ORFNames=MTV012.17c;
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 FUNCTION IN THE BRANCHED-AMINO ACIDS BIOSYNTHESIS, ACTIVITY REGULATION,
RP BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT.
RX PubMed=16111681; DOI=10.1016/j.febslet.2005.07.055;
RA Choi K.J., Yu Y.G., Hahn H.G., Choi J.D., Yoon M.Y.;
RT "Characterization of acetohydroxyacid synthase from Mycobacterium
RT tuberculosis and the identification of its new inhibitor from the screening
RT of a chemical library.";
RL FEBS Lett. 579:4903-4910(2005).
RN [3]
RP ACTIVITY REGULATION.
RX PubMed=18337064; DOI=10.1016/j.ijantimicag.2008.01.016;
RA Sohn H., Lee K.S., Ko Y.K., Ryu J.W., Woo J.C., Koo D.W., Shin S.J.,
RA Ahn S.J., Shin A.R., Song C.H., Jo E.K., Park J.K., Kim H.J.;
RT "In vitro and ex vivo activity of new derivatives of acetohydroxyacid
RT synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous
RT mycobacteria.";
RL Int. J. Antimicrob. Agents 31:567-571(2008).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=19542000; DOI=10.1099/mic.0.029884-0;
RA Awasthy D., Gaonkar S., Shandil R.K., Yadav R., Bharath S., Marcel N.,
RA Subbulakshmi V., Sharma U.;
RT "Inactivation of the ilvB1 gene in Mycobacterium tuberculosis leads to
RT branched-chain amino acid auxotrophy and attenuation of virulence in
RT mice.";
RL Microbiology 155:2978-2987(2009).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, INDUCTION, AND BIOPHYSICOCHEMICAL PROPERTIES.
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 [6]
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. Also
CC involved in condensing pyruvate and 2-ketobutyrate to form 2-aceto-2-
CC hydroxybutyrate. {ECO:0000269|PubMed:16111681,
CC ECO:0000269|PubMed:20884690}.
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 Evidence={ECO:0000269|PubMed:20884690};
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 -!- ACTIVITY REGULATION: Inhibited by valine, sulfometuron methyl (SM),
CC sulfonylureas (SU) and imidazolinones (IM). Pyrazosulfuron ethyl (PSE),
CC promisulfuron methyl (PSM), sulfometuron methyl (SMM), metsulfuron
CC methyl (MSM), and chlorimuron ethyl (CE) inhibited more than 80% of the
CC activity. {ECO:0000269|PubMed:16111681, ECO:0000269|PubMed:18337064}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.76 mM for pyruvate (with the catalytic subunit alone at pH 7.5
CC and at 37 degrees Celsius) {ECO:0000269|PubMed:16111681,
CC ECO:0000269|PubMed:20884690};
CC KM=1.56 mM for pyruvate (with the catalytic and regulatory subunits
CC at pH 7.5 and at 37 degrees Celsius) {ECO:0000269|PubMed:16111681,
CC ECO:0000269|PubMed:20884690};
CC pH dependence:
CC Optimum pH is between 6 and 7. {ECO:0000269|PubMed:16111681,
CC ECO:0000269|PubMed:20884690};
CC Temperature dependence:
CC Optimum temperature is between 35 and 40 degrees Celsius.
CC {ECO:0000269|PubMed:16111681, ECO:0000269|PubMed:20884690};
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:0000305|PubMed:16111681}.
CC -!- INDUCTION: The expression is high during the mid-exponential phase and
CC low during the stationary phase. {ECO:0000269|PubMed:20884690}.
CC -!- DISRUPTION PHENOTYPE: Auxotrophic for all of the 3 branched-chain amino
CC acids (isoleucine, leucine and valine), when grown with either C6 or C2
CC carbon sources. Depletion of these branched chain amino acids in the
CC medium led to loss of viability. {ECO:0000269|PubMed:19542000}.
CC -!- SIMILARITY: Belongs to the TPP enzyme family. {ECO:0000305}.
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DR EMBL; AL123456; CCP45809.1; -; Genomic_DNA.
DR PIR; F70855; F70855.
DR RefSeq; WP_003415168.1; NZ_NVQJ01000041.1.
DR RefSeq; YP_177917.1; NC_000962.3.
DR AlphaFoldDB; P9WG41; -.
DR SMR; P9WG41; -.
DR STRING; 83332.Rv3003c; -.
DR PaxDb; P9WG41; -.
DR DNASU; 887286; -.
DR GeneID; 887286; -.
DR KEGG; mtu:Rv3003c; -.
DR TubercuList; Rv3003c; -.
DR eggNOG; COG0028; Bacteria.
DR OMA; CFGTSGP; -.
DR PhylomeDB; P9WG41; -.
DR BRENDA; 2.2.1.6; 3445.
DR UniPathway; UPA00047; UER00055.
DR UniPathway; UPA00049; UER00059.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005948; C:acetolactate synthase complex; IBA:GO_Central.
DR GO; GO:0009274; C:peptidoglycan-based cell wall; HDA:MTBBASE.
DR GO; GO:0003984; F:acetolactate synthase activity; IDA:MTBBASE.
DR GO; GO:0050660; F:flavin adenine dinucleotide binding; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; IDA:MTBBASE.
DR GO; GO:0030976; F:thiamine pyrophosphate binding; IDA:MTBBASE.
DR GO; GO:0009082; P:branched-chain amino acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009097; P:isoleucine biosynthetic process; IDA:MTBBASE.
DR GO; GO:0009099; P:valine biosynthetic process; IDA:MTBBASE.
DR CDD; cd02015; TPP_AHAS; 1.
DR InterPro; IPR012846; Acetolactate_synth_lsu.
DR InterPro; IPR039368; AHAS_TPP.
DR InterPro; IPR029035; DHS-like_NAD/FAD-binding_dom.
DR InterPro; IPR029061; THDP-binding.
DR InterPro; IPR012000; Thiamin_PyroP_enz_cen_dom.
DR InterPro; IPR012001; Thiamin_PyroP_enz_TPP-bd_dom.
DR InterPro; IPR000399; TPP-bd_CS.
DR InterPro; IPR045229; TPP_enz.
DR InterPro; IPR011766; TPP_enzyme-bd_C.
DR PANTHER; PTHR18968; PTHR18968; 1.
DR Pfam; PF02775; TPP_enzyme_C; 1.
DR Pfam; PF00205; TPP_enzyme_M; 1.
DR Pfam; PF02776; TPP_enzyme_N; 1.
DR SUPFAM; SSF52467; SSF52467; 1.
DR SUPFAM; SSF52518; SSF52518; 2.
DR TIGRFAMs; TIGR00118; acolac_lg; 1.
DR PROSITE; PS00187; TPP_ENZYMES; 1.
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..618
FT /note="Acetolactate synthase large subunit IlvB1"
FT /id="PRO_0000090803"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 429..509
FT /note="Thiamine pyrophosphate binding"
FT BINDING 85
FT /ligand="thiamine diphosphate"
FT /ligand_id="ChEBI:CHEBI:58937"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 293..314
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 336..355
FT /ligand="FAD"
FT /ligand_id="ChEBI:CHEBI:57692"
FT /evidence="ECO:0000250"
FT BINDING 480
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 507
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
SQ SEQUENCE 618 AA; 66123 MW; 9E0523F4AD6EC6AF CRC64;
MSAPTKPHSP TFKPEPHSAA NEPKHPAARP KHVALQQLTG AQAVIRSLEE LGVDVIFGIP
GGAVLPVYDP LFDSKKLRHV LVRHEQGAGH AASGYAHVTG RVGVCMATSG PGATNLVTPL
ADAQMDSIPV VAITGQVGRG LIGTDAFQEA DISGITMPIT KHNFLVRSGD DIPRVLAEAF
HIAASGRPGA VLVDIPKDVL QGQCTFSWPP RMELPGYKPN TKPHSRQVRE AAKLIAAARK
PVLYVGGGVI RGEATEQLRE LAELTGIPVV TTLMARGAFP DSHRQNLGMP GMHGTVAAVA
ALQRSDLLIA LGTRFDDRVT GKLDSFAPEA KVIHADIDPA EIGKNRHADV PIVGDVKAVI
TELIAMLRHH HIPGTIEMAD WWAYLNGVRK TYPLSYGPQS DGSLSPEYVI EKLGEIAGPD
AVFVAGVGQH QMWAAQFIRY EKPRSWLNSG GLGTMGFAIP AAMGAKIALP GTEVWAIDGD
GCFQMTNQEL ATCAVEGIPV KVALINNGNL GMVRQWQSLF YAERYSQTDL ATHSHRIPDF
VKLAEALGCV GLRCEREEDV VDVINQARAI NDCPVVIDFI VGADAQVWPM VAAGTSNDEI
QAARGIRPLF DDITEGHA
