Detailed view for Rv1820

Basic information

TDR Targets ID: 6256
Mycobacterium tuberculosis, Probable acetolactate synthase IlvG (acetohydroxy-acid synthase)(ALS)
Source Database / ID:  Tuberculist 

pI: 5.7326 | Length (AA): 547 | MW (Da): 57521 | Paralog Number: 2

Signal peptide: N | GPI Anchor: | Predicted trans-membrane segments: 0

Druggability Group : DG2

Targets have been classified into druggability groups (DG) according to their druggability score in network driven prioritizations. DGs range from 1 to 5; the higher the group number, the higher the chance of the target to be druggable

Pfam domains

PF00205   Thiamine pyrophosphate enzyme, central domain
PF02775   Thiamine pyrophosphate enzyme, C-terminal TPP binding domain
PF02776   Thiamine pyrophosphate enzyme, N-terminal TPP binding domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0003824   catalytic activity  
GO:0000287   magnesium ion binding  
GO:0030976   thiamin pyrophosphate binding  

Structural information

Modbase 3D models:

There are 4 models calculated for this protein. More info on these models, including the models themselves is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
1 541 1t9b (A) 85 652 22.00 0 1 1.20243 0.02
11 541 4qq8 (A) 4 551 30.00 0 1 1.36585 -0.34
49 155 3lp6 (A) 39 138 33.00 0.36 0.25 0.336212 1.14
192 326 4j1t (C) 275 443 18.00 0 0.72 0.275201 -0.57

Help me make sense of these data.

Target Beg: first modeled residue
Target End: last modeled residue
Template: template structure used for modelling (PDB accession and chain)
Template Beg: first template residue in target-template alignment
Template End: last template residue in target-template alignment
Identity: sequence identity
Evalue: E value for target-template hit
Model Score: GA341 score (>0.7 for reliable model)
MPQS: ModPipe Quality Score (>1.1 for reliable model)
zDope: zDope Score (negative for reliable model)

A more detailed description of these scores is available at the Modbase Model Evaluation Help Pages, and in the papers referenced therein.

PDB Structures:

No structure availble in the PDB for this protein

Expression

Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. murphy
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Dormant phase. hasan
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

Orthologs

Ortholog group members (OG5_126899)

Species Accession Gene Product
Arabidopsis thaliana AT3G48560   acetolactate synthase
Arabidopsis thaliana AT5G17380   2-hydroxyacyl-CoA lyase
Brugia malayi Bm1_25260   Thiamine pyrophosphate enzyme, central domain containing protein
Candida albicans CaO19.9180   Acetolactate synthase
Candida albicans CaO19.1613   Acetolactate synthase
Caenorhabditis elegans CELE_B0334.3   Protein B0334.3, isoform B
Caenorhabditis elegans CELE_T26C12.1   Protein T26C12.1
Dictyostelium discoideum DDB_G0278053   2-hydroxyphytanoyl-CoA lyase
Dictyostelium discoideum DDB_G0292402   hypothetical protein
Dictyostelium discoideum DDB_G0292762   hypothetical protein
Drosophila melanogaster Dmel_CG11208   CG11208 gene product from transcript CG11208-RA
Escherichia coli b0077   acetolactate synthase 3 large subunit
Escherichia coli b3671   acetolactate synthase 2 large subunit
Escherichia coli b2373   oxalyl CoA decarboxylase, ThDP-dependent
Homo sapiens ENSG00000105135   ilvB (bacterial acetolactate synthase)-like
Homo sapiens ENSG00000131373   2-hydroxyacyl-CoA lyase 1
Loa Loa (eye worm) LOAG_13250   ILVBL protein
Loa Loa (eye worm) LOAG_11696   thiamine pyrophosphate enzyme
Mycobacterium leprae ML2083c   Probable Acetolactate synthase IlvG (Acetohydroxy-acid synthase)(ALS)
Mycobacterium leprae ML1696c   PROBABLE ACETOLACTATE SYNTHASE (LARGE SUBUNIT) ILVB (ACETOHYDROXY-ACID SYNTHASE)
Mus musculus ENSMUSG00000032763   ilvB (bacterial acetolactate synthase)-like
Mus musculus ENSMUSG00000021884   2-hydroxyacyl-CoA lyase 1
Mycobacterium tuberculosis Rv3003c   Acetolactate synthase (large subunit) IlvB1 (acetohydroxy-acid synthase)
Mycobacterium tuberculosis Rv1820   Probable acetolactate synthase IlvG (acetohydroxy-acid synthase)(ALS)
Mycobacterium tuberculosis Rv0118c   Probable oxalyl-CoA decarboxylase OxcA
Mycobacterium ulcerans MUL_3039   hypothetical protein
Mycobacterium ulcerans MUL_1947   acetolactate synthase 1 catalytic subunit
Mycobacterium ulcerans MUL_4804   putative oxalyl-CoA decarboxylase
Oryza sativa 4329450   Os02g0510200
Oryza sativa 4324491   Os01g0505400
Saccharomyces cerevisiae YEL020C   putative indolepyruvate decarboxylase family protein
Saccharomyces cerevisiae YMR108W   acetolactate synthase catalytic subunit
Schistosoma japonicum Sjp_0099100   ko:K01651 acetolactate synthase [EC2.2.1.6], putative
Schistosoma japonicum Sjp_0100320   ko:K01651 acetolactate synthase [EC2.2.1.6], putative
Schistosoma mansoni Smp_005390.2   acetolactate synthase
Schistosoma mansoni Smp_005390.1   acetolactate synthase
Schmidtea mediterranea mk4.052684.01   Acetolactate synthase-like protein
Schmidtea mediterranea mk4.007232.00   Acetolactate synthase-like protein
Schmidtea mediterranea mk4.003659.01   Acetolactate synthase

Essentiality

Rv1820 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1850 this record Mycobacterium tuberculosis non-essential nmpdr
mtu119 Mycobacterium tuberculosis essential nmpdr
b0077 Escherichia coli non-essential goodall
b2373 Escherichia coli non-essential goodall
b3671 Escherichia coli non-essential goodall
CELE_T26C12.1 Caenorhabditis elegans embryonic lethal wormbase
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • goodall The Essential Genome of Escherichia coli K-12 (Transposon directed high-throughput mutagenesis) Goodall, Emily CA, et al. "The essential genome of Escherichia coli K-12." mBio 9.1 (2018): e02096-17.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • plasmo Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes. Bushell, Ellen, et al. "Functional profiling of a Plasmodium genome reveals an abundance of essential genes." Cell 170.2 (2017): 260-272.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • sidik A Genome-wide CRISPR Screen in Toxoplasma Identifies Essential Apicomplexan Genes. Sidik, Saima M., et al. "A genome-wide CRISPR screen in toxoplasma identifies essential apicomplexan genes." Cell 166.6 (2016): 1423-1435.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

In TDR Targets, information about phenotypes that are caused by drugs, or by genetic manipulation of cells (e.g. gene knockouts or knockdowns) is manually curated from the literature. These descriptions help to describe the potential of the target for drug development. If no information is available for this gene or if the information is incomplete, this may mean that i) the papers containing this information either appeared after the curation effort for this organism was carried out or they were inadvertently missed by curators; or that ii) the curation effort for this organism has not yet started.

In any case, if you have information about papers containing relevant validation data for this target, please contact us.

Annotated validation

No validation data for this target

Associated compounds / Druggability

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Saccharomyces cerevisiae acetolactate synthase catalytic subunit Compounds References
Bromus tectorum Acetolactate synthase Compounds References
Raphanus raphanistrum Acetolactate synthase Compounds References
Zea mays Acetolactate synthase Compounds References
Arabidopsis thaliana acetolactate synthase Compounds References
Lolium rigidum Acetolactate synthase Compounds References
Nicotiana tabacum Acetolactate synthase Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.059 1 1
0.0398 0.4136 1
0.0342 0.3204 1
0.0372 0.6976 1
0.0443 0.4846 1
0.0449 1 1
0.0466 0.5333 1
0.0554 1 1
0.0461 1 1
0.0799 0.6762 1
0.022 1 1
0.0435 1 1
0.0435 1 1
0.0785 0.8648 1
0.0435 1 1
0.0449 1 1
0.0435 1 1
0.0133 1 1
0.0133 1 1
0.0808 1 1
0.0228 1 1
0.123 1 1
0.0435 1 1
0.0341 0.3653 1
0.0492 0.509 1
0.0228 1 1
0.077 1 1
0.0474 0.5253 1
0.0341 0.4884 1
0.0255 0.6957 1
0.0245 1 1
0.0435 1 1
0.1385 1 1
0.0435 1 1
0.0435 1 1
0.0128 1 1
0.0783 1 1
0.0266 0.3735 1
0.0554 1 1
0.0385 1 1
0.0341 1 1
0.0228 0.4926 1
0.0675 1 1
0.012 0.5884 1
0.0769 1 1
0.0326 0.3191 1
0.0232 1 1
0.0133 1 1
0.0133 0.7054 1
0.0133 1 1
0.0569 0.6559 1
0.0326 0.426 1
0.0266 0.2739 0.2631
0.0222 1 1
0.0133 0.8542 1
0.011 0.3066 0.2829
0.0259 0.2783 1
0.1393 1 1
0.0675 0.7894 1
0.0133 0.603 1
0.0224 0.34 1
0.0544 1 1
0.0224 0.34 1
0.0358 1 1
0.147 1 1
0.0232 0.6353 1
0.0492 0.509 1
0.0255 0.4874 1
0.0449 1 1
0.0385 1 1
0.0234 0.8344 1
0.0558 0.5567 1
0.1161 1 1
0.0359 0.8528 0.8451
0.012 0.5884 1
0.0439 0.9727 1
0.0571 1 1
0.0577 0.6946 1
0.1006 1 1
0.0133 0.8542 1
0.0899 1 1
0.0357 1 1
0.0133 1 1
0.0554 1 1
0.0233 1 1
0.0133 0.4005 0.9497
0.0256 0.8811 1
0.0133 1 1
0.0218 1 1
0.0379 1 1
0.0463 0.4408 1
0.0439 0.9727 1
0.0884 1 1
0.0577 0.6946 1
0.0133 1 1
0.0122682 1 1
0.0133 0.3966 1
0.0243 1 1
0.0671 1 1
0.0266 0.3287 1
0.0435 1 1
0.0218 1 1
0.0133 1 1
0.0229 0.7711 1
0.0228 0.4926 1
0.0246 0.4041 1
0.0435 1 1
0.0334 1 1
0.0354 0.5525 1
0.0435 1 1
0.0398 0.4424 1
0.1205 1 1
0.0552 1 1
0.0232 1 1
0.0241 1 1
0.0435 1 1
0.045 1 1
0.0761 1 1
0.0133 0.3236 1
0.0783 1 1
0.0234 0.8009 1
0.0435 1 1
0.0259 1 1
0.0802 1 1
0.043 1 1
0.0266 0.3735 1
0.1137 1 1
0.0325 1 1
0.0213 1 1
0.0336 1 1
0.0133 1 1
0.0435 1 1
0.0133 0.5628 1
0.0457 0.537 1
0.0266 1 1
0.1157 1 1
0.0577 0.6946 1
0.1146 1 1
0.0329 0.4343 1
0.0821 1 1
0.0769 1 1
0.1127 1 1
0.0435 1 1
0.0511 1 1
0.0215 1 1
0.0621 0.6524 1
0.023 1 1
0.0435 1 1
0.0133 1 1
0.0329 1 1

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier Rv1820 (Mycobacterium tuberculosis), Probable acetolactate synthase IlvG (acetohydroxy-acid synthase)(ALS)
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