Detailed view for Tb927.9.12110

Basic information

TDR Targets ID: 12199
Trypanosoma brucei, 6-phosphogluconate dehydrogenase, decarboxylating

Source Database / ID:  TriTrypDB  GeneDB

pI: 7.8868 | Length (AA): 479 | MW (Da): 52166 | Paralog Number: 0

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

Druggability Group : DG3

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

PF00393   6-phosphogluconate dehydrogenase, C-terminal domain
PF03446   NAD binding domain of 6-phosphogluconate dehydrogenase

Gene Ontology

Mouse over links to read term descriptions.
GO:0004616   phosphogluconate dehydrogenase (decarboxylating) activity  
GO:0005488   binding  
GO:0003824   catalytic activity  
GO:0050662   coenzyme binding  
GO:0050661   NADP binding  
GO:0016491   oxidoreductase activity  
GO:0006098   pentose-phosphate shunt  
GO:0055114   oxidation reduction  
GO:0008152   metabolic process  

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
2 479 1pgj (A) 1 478 99.99 0 1 2.21291 -1.26

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:

  • 1PGJ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% 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_127175)

Species Accession Gene Product
Arabidopsis thaliana AT3G02360   6-phosphogluconate dehydrogenase, decarboxylating 3
Arabidopsis thaliana AT5G41670   6-phosphogluconate dehydrogenase, decarboxylating 2
Arabidopsis thaliana AT1G64190   6-phosphogluconate dehydrogenase, decarboxylating 1
Babesia bovis BBOV_IV004060   6-phosphogluconate dehydrogenase, putative
Brugia malayi Bm1_52945   6-phosphogluconate dehydrogenase, decarboxylating, putative
Candida albicans CaO19.12491   similar to S. cerevisiae GND1 (YHR183W) and GND2 (YGR256W) 6-phosphogluconate dehydrogenase
Candida albicans CaO19.5024   similar to S. cerevisiae GND1 (YHR183W) and GND2 (YGR256W) 6-phosphogluconate dehydrogenase
Chlamydia trachomatis CT_063   6-phosphogluconate dehydrogenase
Dictyostelium discoideum DDB_G0277885   6-phosphogluconate dehydrogenase
Drosophila melanogaster Dmel_CG3724   Phosphogluconate dehydrogenase
Escherichia coli b2029   6-phosphogluconate dehydrogenase, decarboxylating
Echinococcus granulosus EgrG_000846400   6 phosphogluconate dehydrogenase
Echinococcus multilocularis EmuJ_000846400   6 phosphogluconate dehydrogenase
Giardia lamblia GL50803_14759   6-phosphogluconate dehydrogenase, decarboxylating
Homo sapiens 378708   apoptosis-inducing, TAF9-like domain 1
Homo sapiens ENSG00000142657   phosphogluconate dehydrogenase
Leishmania braziliensis LbrM.34.3250   6-phosphogluconate dehydrogenase, decarboxylating, putative
Leishmania donovani LdBPK_353390.1   6-phosphogluconate dehydrogenase, decarboxylating, putative
Leishmania infantum LinJ.35.3390   6-phosphogluconate dehydrogenase, decarboxylating, putative
Leishmania major LmjF.35.3340   6-phosphogluconate dehydrogenase, decarboxylating, putative
Leishmania mexicana LmxM.34.3340   6-phosphogluconate dehydrogenase, decarboxylating, putative
Loa Loa (eye worm) LOAG_08072   pgd protein
Mycobacterium leprae ML2065   PROBABLE 6-PHOSPHOGLUCONATE DEHYDROGENASE GND1
Mus musculus ENSMUSG00000028961   phosphogluconate dehydrogenase
Mycobacterium tuberculosis Rv1844c   Probable 6-phosphogluconate dehydrogenase Gnd1
Mycobacterium tuberculosis Rv1122   Probable 6-phosphogluconate dehydrogenase, decarboxylating Gnd2
Mycobacterium ulcerans MUL_3035   6-phosphogluconate dehydrogenase
Mycobacterium ulcerans MUL_0148   6-phosphogluconate dehydrogenase
Neospora caninum NCLIV_060600   6-phosphogluconate dehydrogenase, decarboxylating (EC 1.1.1.44), related
Neospora caninum NCLIV_017630   6-phosphogluconate dehydrogenase, decarboxylating (EC 1.1.1.44), related
Oryza sativa 4350528   Os11g0484500
Oryza sativa 4339892   Os06g0111500
Plasmodium berghei PBANKA_1318400   6-phosphogluconate dehydrogenase, decarboxylating, putative
Plasmodium falciparum PF3D7_1454700   6-phosphogluconate dehydrogenase, decarboxylating, putative
Plasmodium knowlesi PKNH_1227400   6-phosphogluconate dehydrogenase, decarboxylating, putative
Plasmodium vivax PVX_117745   6-phosphogluconate dehydrogenase, decarboxylating, putative
Plasmodium yoelii PY00858   6-phosphogluconate dehydrogenase, decarboxylating
Saccharomyces cerevisiae YHR183W   phosphogluconate dehydrogenase (decarboxylating) GND1
Saccharomyces cerevisiae YGR256W   phosphogluconate dehydrogenase (decarboxylating) GND2
Schistosoma japonicum Sjp_0030250   ko:K00033 6-phosphogluconate dehydrogenase [EC1.1.1.44], putative
Schistosoma mansoni Smp_071840   6-phosphogluconate dehydrogenase
Schmidtea mediterranea mk4.000036.04   6-phosphogluconate dehydrogenase,putative
Schmidtea mediterranea mk4.000036.05   6-phosphogluconate dehydrogenase, decarboxylating
Schmidtea mediterranea mk4.000036.06   6-phosphogluconate dehydrogenase,putative
Schmidtea mediterranea mk4.002185.02   6-phosphogluconate dehydrogenase,putative
Trypanosoma brucei gambiense Tbg972.9.7350   6-phosphogluconate dehydrogenase, decarboxylating, putative
Trypanosoma brucei Tb927.9.12110   6-phosphogluconate dehydrogenase, decarboxylating
Trypanosoma congolense TcIL3000_9_4990   6-phosphogluconate dehydrogenase, decarboxylating, putative
Trypanosoma cruzi TcCLB.507011.269   6-phosphogluconate dehydrogenase, decarboxylating
Trypanosoma cruzi TcCLB.510663.70   6-phosphogluconate dehydrogenase, decarboxylating, putative
Toxoplasma gondii TGME49_242600   6-phosphogluconate dehydrogenase
Toxoplasma gondii TGME49_307850   6-phosphogluconate dehydrogenase
Treponema pallidum TP0331   6-phosphogluconate dehydrogenase
Theileria parva TP01_0193   6-phosphogluconate dehydrogenase, putative
Trichomonas vaginalis TVAG_553420   6-phosphogluconate dehydrogenase, putative
Trichomonas vaginalis TVAG_006140   6-phosphogluconate dehydrogenase, putative
Trichomonas vaginalis TVAG_273380   3-hydroxyisobutyrate dehydrogenase, putative

Essentiality

Tb927.9.12110 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1874 Mycobacterium tuberculosis non-essential nmpdr
mtu1142 Mycobacterium tuberculosis essential nmpdr
Tb09.211.3180 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (3 days) alsford
Tb09.211.3180 this record Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb09.211.3180 this record Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb09.211.3180 this record Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b2029 Escherichia coli non-essential goodall
PBANKA_1318400 Plasmodium berghei Essential plasmo
TGME49_307850 Toxoplasma gondii Essentiality uncertain sidik
TGME49_242600 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930

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: ** unpublished observation. References: 11966468
cell proliferation (GO:0008283) decreased (PATO:0000468) 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: decreased cell proliferation (significant loss of fitness) in bloodstream forms (stage 6 days). 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

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Homo sapiens phosphogluconate dehydrogenase Compounds References
Ovis aries 6-phosphogluconate dehydrogenase, decarboxylating 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
0.0124 0.3099 0.3355
0.0696 1 1
0.0121 1 0.5
0.0124 0.3337 0.3439
0.0757 1 0.5
0.0184 1 1
0.0129 1 1
0.0757 1 0.5
0.0127 0.3467 0.3561
0.0184 1 1
0.0218 1 0.5
0.0187 0.5877 0.5
0.0124 0.3643 0.3757
0.0117 0.3262 0.3333
0.0184 1 1
0.0696 1 1
0.0129 0.3932 0.4001
0.0218 1 0.5
0.0117 0.3653 0.3511
0.0117 0.3653 0.3511
0.0257 1 1
0.0117 0.3653 0.3511
0.0184 0.3846 0.5
0.0071 0.452 0.452
0.0237 0.2553 0.2553

Assayability

Assay information

  • Assay for 6-Phosphogluconic Dehydrogenase pH 7.5 (1.1.1.44 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • ChEMBL
  • Inhibition of Trypanosoma brucei 6-phosphogluconate dehydrogenase
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Trypanosoma brucei ( 3 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    Tb927.9.12110 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Trypanosoma brucei ( 2 )

Bibliographic References

1 literature reference was collected for this gene.

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Gene identifier Tb927.9.12110 (Trypanosoma brucei), 6-phosphogluconate dehydrogenase, decarboxylating
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