Detailed view for Tb927.2.4370

Basic information

TDR Targets ID: 55156
Trypanosoma brucei, trypanothione synthetase
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.0541 | Length (AA): 627 | MW (Da): 71613 | Paralog Number: 1

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

Druggability Group : DG4

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

PF03738   Glutathionylspermidine synthase preATP-grasp
PF05257   CHAP domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0019342   trypanothione biosynthetic process  
GO:0015042   trypanothione-disulfide reductase activity  
GO:0005829   cytosol  

Metabolic Pathways

Glutathione metabolism (KEGG)
Global map (KEGG)

Structural information

Modbase 3D models:

There is 1 model calculated for this protein. More info on this model, including the model itself is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
8 626 2vob (B) 10 643 61.00 0 1 1.64824 -0.52

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
Upper 60-80% percentile Procyclic, Bloodstream Form. Siegel TN
Show/Hide expression data references
  • Siegel TN Genome-wide analysis of mRNA abundance in two life-cycle stages of Trypanosoma brucei and identification of splicing and polyadenylation sites.

Orthologs

Ortholog group members (OG5_134306)

Species Accession Gene Product
Escherichia coli b3038   ATP-Grasp family ATPase
Escherichia coli b4186   ATP-Grasp family ATPase
Escherichia coli b2988   fused glutathionylspermidine amidase/glutathionylspermidine synthetase
Leishmania braziliensis LbrM.27.2010   trypanothione synthetase, putative
Leishmania donovani LdBPK_271770.1   trypanothione synthetase
Leishmania infantum LinJ.27.1770   trypanothione synthetase, putative
Leishmania major LmjF.27.1870   trypanothione synthetase, putative
Leishmania mexicana LmxM.27.1870   trypanothione synthetase, putative
Trypanosoma brucei gambiense Tbg.972.2.2440   trypanothione synthetase, putative
Trypanosoma brucei Tb11.v5.0653   trypanothione synthetase, putative
Trypanosoma brucei Tb927.2.4370   trypanothione synthetase
Trypanosoma congolense TcIL3000_2_770   trypanothione synthetase
Trypanosoma cruzi TcCLB.509099.50   trypanothione synthetase
Trypanosoma cruzi TcCLB.509319.90   trypanothione synthetase

Essentiality

Tb927.2.4370 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
Tb927.2.4370 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.2.4370 this record Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.2.4370 this record Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.2.4370 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b2988 Escherichia coli non-essential goodall
b3038 Escherichia coli non-essential goodall
b4186 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) single cell organism (CARO:0000064) bloodstream stage (PLO:0040) inferred from RNAi experiment (ECO:0000019) Trypanosoma brucei brucei No drug identifiers listed for this gene.
Annotator: ts4@sanger.ac.uk. Comment: . References: 15110394
cell proliferation (GO:0008283) normal (PATO:0000461) bloodstream stage trypomastigotes (PLO:0027) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in bloodstream forms (stage 6 days). References: 21363968
cell proliferation (GO:0008283) normal (PATO:0000461) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: normal cell proliferation (no significant loss or gain of fitness) in procyclic forms . References: 21363968
cell proliferation (GO:0008283) decreased (PATO:0000468) procyclic (PLO:0034) inferred from RNAi experiment (ECO:0000019) No drug identifiers listed for this gene.
Annotator: fernan@iib.unsam.edu.ar. Comment: decreased cell proliferation (significant loss of fitness) in differentiation of procyclic to bloodstream forms . References: 21363968

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
Non orthologous druggable targets
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets
Obtained from network model
No druggable targets predicted through repurposing network model

Assayability

Assay information

  • ChEMBL
  • Inhibition of Trypanosoma brucei brucei trypanothione synthetase assessed as residual activity at 30 uM after 30 mins incubation by scintillation counting analysis

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.2.4370 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Trypanosoma brucei ( 2 )

Bibliographic References

11 literature references were collected for this gene.

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Gene identifier Tb927.2.4370 (Trypanosoma brucei), trypanothione synthetase
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