P0A622 (ILVB1_MYCTU) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Acetolactate synthase large subunit IlvB1
Short name=ALS
EC=2.2.1.6

Alternative name(s):
Acetohydroxy-acid synthase large subunit
Short name=AHAS

Gene names

Name:	ilvB1
Ordered Locus Names:	Rv3003c, MT3083
ORF Names:	MTV012.17c

Organism

Mycobacterium tuberculosis

Taxonomic identifier

1773 [NCBI]

Taxonomic lineage

Bacteria › Actinobacteria › Actinobacteridae › Actinomycetales › Corynebacterineae › Mycobacteriaceae › Mycobacterium › Mycobacterium tuberculosis complex

Protein attributes

Sequence length	618 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the conversion of 2 pyruvate molecules into acetolactate in the first common step of the biosynthetic pathway of the branched-amino acids such as leucine, isoleucine, and valine. Also involved in condensing pyruvate and 2-ketobutyrate to form 2-aceto-2-hydroxybutyrate. Ref.3
Catalytic activity	2 pyruvate = 2-acetolactate + CO2.
Cofactor	Binds 1 magnesium ion per subunit By similarity. Binds 1 thiamine pyrophosphate per subunit By similarity.
Enzyme regulation	Inhibited by valine, sulfometuron methyl (SM), sulfonylureas (SU) and imidazolinones (IM). Pyrazosulfuron ethyl (PSE), promisulfuron methyl (PSM), sulfometuron methyl (SMM), metsulfuron methyl (MSM), and chlorimuron ethyl (CE) inhibited more than 80% of the activity. Ref.3 Ref.4
Pathway	Amino-acid biosynthesis; L-isoleucine biosynthesis; L-isoleucine from 2-oxobutanoate: step 1/4. Amino-acid biosynthesis; L-valine biosynthesis; L-valine from pyruvate: step 1/4.
Subunit structure	Heterodimer of large catalytic subunit and small regulatory subunit Probable. Ref.3
Disruption phenotype	Auxotrophic for all of the 3 branched-chain amino acids (isoleucine, leucine and valine), when grown with either C6 or C2 carbon sources. Depletion of these branched chain amino acids in the medium led to loss of viability. Ref.5
Sequence similarities	Belongs to the TPP enzyme family.
Biophysicochemical properties	Kinetic parameters: KM=2.76 mM for pyruvate (with the catalytic subunit alone at pH 7.5 and at 37 degrees Celsius) Ref.3 KM=1.56 mM for pyruvate (with the catalytic and regulatory subunits at pH 7.5 and at 37 degrees Celsius)

Ontologies

Keywords
Biological process	Amino-acid biosynthesis Branched-chain amino acid biosynthesis
Ligand	FAD Flavoprotein Magnesium Metal-binding Thiamine pyrophosphate
Molecular function	Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	growth Inferred from mutant phenotype. Source: MTBBASE isoleucine biosynthetic process Inferred from mutant phenotype Ref.5. Source: UniProtKB valine biosynthetic process Inferred from mutant phenotype Ref.5. Source: UniProtKB
Molecular function	acetolactate synthase activity Inferred from direct assay Ref.3. Source: MTBBASE flavin adenine dinucleotide binding Inferred from electronic annotation. Source: InterPro magnesium ion binding Inferred from direct assay Ref.3. Source: MTBBASE thiamine binding Inferred from direct assay Ref.3. Source: MTBBASE thiamine pyrophosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 618	618	Acetolactate synthase large subunit IlvB1		PRO_0000090803
Regions
	Nucleotide binding	293 – 314	22	FAD By similarity
	Nucleotide binding	336 – 355	20	FAD By similarity
	Region	429 – 509	81	Thiamine pyrophosphate binding
Sites
	Metal binding	480	1	Magnesium By similarity
	Metal binding	507	1	Magnesium By similarity
	Binding site	85	1	Thiamine pyrophosphate By similarity
	Binding site	187	1	FAD By similarity

Sequences

	Sequence		Length	Mass (Da)
	P0A622 [UniParc]. Last modified March 15, 2005. Version 1. Checksum: 9E0523F4AD6EC6AF	FASTA	618	66,123
	10 20 30 40 50 60 MSAPTKPHSP TFKPEPHSAA NEPKHPAARP KHVALQQLTG AQAVIRSLEE LGVDVIFGIP 70 80 90 100 110 120 GGAVLPVYDP LFDSKKLRHV LVRHEQGAGH AASGYAHVTG RVGVCMATSG PGATNLVTPL 130 140 150 160 170 180 ADAQMDSIPV VAITGQVGRG LIGTDAFQEA DISGITMPIT KHNFLVRSGD DIPRVLAEAF 190 200 210 220 230 240 HIAASGRPGA VLVDIPKDVL QGQCTFSWPP RMELPGYKPN TKPHSRQVRE AAKLIAAARK 250 260 270 280 290 300 PVLYVGGGVI RGEATEQLRE LAELTGIPVV TTLMARGAFP DSHRQNLGMP GMHGTVAAVA 310 320 330 340 350 360 ALQRSDLLIA LGTRFDDRVT GKLDSFAPEA KVIHADIDPA EIGKNRHADV PIVGDVKAVI 370 380 390 400 410 420 TELIAMLRHH HIPGTIEMAD WWAYLNGVRK TYPLSYGPQS DGSLSPEYVI EKLGEIAGPD 430 440 450 460 470 480 AVFVAGVGQH QMWAAQFIRY EKPRSWLNSG GLGTMGFAIP AAMGAKIALP GTEVWAIDGD 490 500 510 520 530 540 GCFQMTNQEL ATCAVEGIPV KVALINNGNL GMVRQWQSLF YAERYSQTDL ATHSHRIPDF 550 560 570 580 590 600 VKLAEALGCV GLRCEREEDV VDVINQARAI NDCPVVIDFI VGADAQVWPM VAAGTSNDEI 610 QAARGIRPLF DDITEGHA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence." Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K. , Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S., Barrell B.G. Nature 393:537-544(1998) [PubMed: 9634230] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 25618 / H37Rv.
[2]	"Whole-genome comparison of Mycobacterium tuberculosis clinical and laboratory strains." Fleischmann R.D., Alland D., Eisen J.A., Carpenter L., White O., Peterson J.D., DeBoy R.T., Dodson R.J., Gwinn M.L., Haft D.H., Hickey E.K., Kolonay J.F., Nelson W.C., Umayam L.A., Ermolaeva M.D., Salzberg S.L., Delcher A., Utterback T.R. , Weidman J.F., Khouri H.M., Gill J., Mikula A., Bishai W., Jacobs W.R. Jr., Venter J.C., Fraser C.M. J. Bacteriol. 184:5479-5490(2002) [PubMed: 12218036] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: CDC 1551 / Oshkosh.
[3]	"Characterization of acetohydroxyacid synthase from Mycobacterium tuberculosis and the identification of its new inhibitor from the screening of a chemical library." Choi K.J., Yu Y.G., Hahn H.G., Choi J.D., Yoon M.Y. FEBS Lett. 579:4903-4910(2005) [PubMed: 16111681] [Abstract] Cited for: FUNCTION IN THE BRANCHED-AMINO ACIDS BIOSYNTHESIS, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
[4]	"In vitro and ex vivo activity of new derivatives of acetohydroxyacid synthase inhibitors against Mycobacterium tuberculosis and non-tuberculous mycobacteria." Sohn H., Lee K.S., Ko Y.K., Ryu J.W., Woo J.C., Koo D.W., Shin S.J., Ahn S.J., Shin A.R., Song C.H., Jo E.K., Park J.K., Kim H.J. Int. J. Antimicrob. Agents 31:567-571(2008) [PubMed: 18337064] [Abstract] Cited for: ENZYME REGULATION.
[5]	"Inactivation of the ilvB1 gene in Mycobacterium tuberculosis leads to branched-chain amino acid auxotrophy and attenuation of virulence in mice." Awasthy D., Gaonkar S., Shandil R.K., Yadav R., Bharath S., Marcel N., Subbulakshmi V., Sharma U. Microbiology 155:2978-2987(2009) [PubMed: 19542000] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	BX842581 Genomic DNA. Translation: CAE55537.1. AE000516 Genomic DNA. Translation: AAK47412.1.
PIR	F70855.
RefSeq	NP_337598.1. NC_002755.2. YP_177917.1. NC_000962.2.
3D structure databases
ProteinModelPortal	P0A622.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblBacteria	EBMYCT00000003781; EBMYCP00000003781; EBMYCG00000003779. EBMYCT00000072990; EBMYCP00000071049; EBMYCG00000072985.
GeneID	887286. 926690.
GenomeReviews	Gene locus MT3083 in contig AE000516_GR. Gene locus Rv3003c in contig AL123456_GR.
KEGG	mtc:MT3083. mtu:Rv3003c.
PATRIC	18128546. VBIMycTub22151_3371.
TIGR	MT3083.
Organism-specific databases
TubercuList	Rv3003c.
Phylogenomic databases
GeneTree	EBGT00050000014643.
HOGENOM	HBG323037.
OMA	HSWRYDH.
PhylomeDB	P0A622.
ProtClustDB	PRK07789.
Family and domain databases
InterPro	IPR012846. Acetolactate_synth_lsu. IPR012000. Thiamin_PyroP_enz_cen_dom. IPR012001. Thiamin_PyroP_enz_TPP-bd_dom. IPR000399. TPP-bd_CS. IPR011766. TPP_enzyme-bd_C. [Graphical view]
KO	K01652.
PANTHER	PTHR18968:SF13. PTHR18968:SF13. 1 hit.
Pfam	PF02775. TPP_enzyme_C. 1 hit. PF00205. TPP_enzyme_M. 1 hit. PF02776. TPP_enzyme_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR00118. Acolac_lg. 1 hit.
PROSITE	PS00187. TPP_ENZYMES. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

ILVB1_MYCTU

Accession

Primary (citable) accession number: P0A622
Secondary accession number(s): O53250

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	January 25, 2012
This is version 44 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program