Detailed view for Rv3913

Basic information

TDR Targets ID: 9997
Mycobacterium tuberculosis, Probable thioredoxin reductase TrxB2 (TRXR) (TR)

Source Database / ID:  Tuberculist 

pI: 5.2166 | Length (AA): 335 | MW (Da): 35643 | Paralog Number: 0

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

PF07992   Pyridine nucleotide-disulphide oxidoreductase

Gene Ontology

Mouse over links to read term descriptions.
GO:0005737   cytoplasm  
GO:0016491   oxidoreductase activity  
GO:0009055   electron carrier activity  
GO:0004791   thioredoxin-disulfide reductase activity  
GO:0055114   oxidation reduction  
GO:0019430   removal of superoxide radicals  

Metabolic Pathways

Structural information

Modbase 3D models:

There are 2 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
10 322 2a87 (A) 10 322 99.99 0 1 2.11373 -0.89
15 52 5dbj (E) 6 43 45.00 0.0051 0.22 0.456433 0.97

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:

  • 2A87:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. murphy
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_127532)

Species Accession Gene Product
Arabidopsis thaliana AT2G41680   NADPH-dependent thioredoxin reductase C
Arabidopsis thaliana AT2G17420   NADPH-dependent thioredoxin reductase A
Arabidopsis thaliana AT4G35460   thioredoxin reductase 1
Candida albicans CaO19.4290   single gene similar to S. cerevisiae TRR1 (YDR353W) and TRR2 (YHR106W) cytoplasmic and mitochondrial thioredoxin reductases
Candida albicans CaO19.11766   single gene similar to S. cerevisiae TRR1 (YDR353W) and TRR2 (YHR106W) cytoplasmic and mitochondrial thioredoxin reductases
Chlamydia trachomatis CT_099   thioredoxin reductase
Dictyostelium discoideum DDB_G0280815   thioredoxin reductase
Escherichia coli b0888   thioredoxin reductase, FAD/NAD(P)-binding
Entamoeba histolytica EHI_155440   thioredoxin reductase, putative
Giardia lamblia GL50803_9827   Thioredoxin reductase
Mycobacterium leprae ML2703   THIOREDOXIN TRXC (TRX) (MPT46)
Mycobacterium tuberculosis Rv3913   Probable thioredoxin reductase TrxB2 (TRXR) (TR)
Mycobacterium ulcerans MUL_5066   thioredoxin reductase TrxB2
Oryza sativa 4330505   Os02g0713400
Oryza sativa 4340912   Os06g0327300
Oryza sativa 4344159   Os07g0657900
Saccharomyces cerevisiae YHR106W   thioredoxin-disulfide reductase TRR2
Saccharomyces cerevisiae YDR353W   thioredoxin-disulfide reductase TRR1
Treponema pallidum TP0814   thioredoxin reductase (trxB)
Trichomonas vaginalis TVAG_125360   disulfide oxidoreductase, putative
Trichomonas vaginalis TVAG_474980   dihydrolipoamide dehydrogenase, putative
Trichomonas vaginalis TVAG_240530   disulfide oxidoreductase, putative
Trichomonas vaginalis TVAG_281360   disulfide oxidoreductase, putative
Trichomonas vaginalis TVAG_348010   disulfide oxidoreductase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0566   thioredoxin reductase

Essentiality

Rv3913 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu3980 this record Mycobacterium tuberculosis essential nmpdr
b0888 Escherichia coli non-essential goodall
YDR353W Saccharomyces cerevisiae inviable yeastgenome
Show/Hide essentiality data references
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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

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

Druggability index (range: 0 to 1): 0.5


Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Entamoeba histolytica thioredoxin reductase, putative Compounds References
Escherichia coli thioredoxin reductase, FAD/NAD(P)-binding 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
0.0309 0.3473 1
0.0297 0.3641 1
0.0674 0.2955 0.3702
0.0307 0.3598 1
0.0178 0.886 1
0.0309 0.3694 1
0.1837 1 1
0.0171 0.3106 0.5
0.2066 1 1
0.0139 0.5338 1
0.0311 0.348 1
0.0153 0.419 1
0.1825 1 1
0.0323 0.3474 1
0.0173 0.5884 1
0.0289 1 1
0.0143 0.3844 0.5887
0.0684 0.2531 0.314
0.2034 1 1
0.2043 1 1
0.0683 0.2794 0.3364
0.1998 1 1
0.0309 0.3473 1
0.0148 0.2738 0.6017
0.0161 0.4066 0.6126
0.0139 0.2791 0.2756
0.0328 0.3574 1
0.0144 0.3052 0.6084
0.0145 0.3956 0.9883
0.0674 0.2955 0.3702
0.0462 0.729 0.9101
0.0178 0.886 1
0.0627 0.6547 1
0.1958 1 0.5
0.0674 0.2955 0.3702
0.0621 0.6816 1
0.0302 0.3489 1
0.0171 0.2813 0.5926
0.2076 1 1
0.0152 0.259 0.5699
0.0145 0.3269 0.6084
0.0152 0.259 0.5699
0.0674 0.2955 0.3702
0.0674 0.2955 0.3702
0.1868 1 1
0.2076 1 1
0.0319 0.3594 1
0.0684 0.2531 0.314
0.0155 0.2614 0.6088
0.2074 1 1
0.0144 0.3963 0.5887
0.1958 1 0.5
0.0649 0.4288 0.6766
0.2066 1 1

Assayability

Assay information

  • Assay for Thioredoxin Reductase (1.6.4.5 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis TrxR at 5 uM after 10 mins by microplate reader analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis TrxR at 1.67 uM after 10 mins by microplate reader analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis TrxR after 10 mins by microplate reader analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis TrxR at 45 uM after 10 mins by microplate reader analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis TrxR at 15 uM after 10 mins by microplate reader analysis

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier Rv3913 (Mycobacterium tuberculosis), Probable thioredoxin reductase TrxB2 (TRXR) (TR)
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