Detailed view for LmjF.24.0850

Basic information

TDR Targets ID: 25110
Leishmania major, triosephosphate isomerase
Source Database / ID:  TriTrypDB  GeneDB

pI: 8.4677 | Length (AA): 251 | MW (Da): 27195 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | 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

PF00121   Triosephosphate isomerase

Gene Ontology

Mouse over links to read term descriptions.
GO:0003824   catalytic activity  
GO:0004807   triose-phosphate isomerase activity  
GO:0008152   metabolic process  
GO:0006096   glycolysis  

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
3 251 1sw0 (A) 2 248 51.00 0 1 1.68 -2.12
3 251 1kv5 (A) 2 250 69.00 0 1 2.02 -2.51
3 251 1n55 (A) 2 250 92.00 0 1 2.13 -2.49
3 251 5cg7 (A) 3 251 92.00 0 1 2.17063 -1.89

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:

PDB tag
  • 1AMK:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1IF2:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1N55:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1QDS:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2VXN:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile amastigotes, metacyclic. Fernandes MC
Show/Hide expression data references
  • Fernandes MC Dual Transcriptome Profiling of Leishmania-Infected Human Macrophages Reveals Distinct Reprogramming Signatures.

Orthologs

Ortholog group members (OG5_127002)

Species Accession Gene Product
Arabidopsis thaliana AT2G21170   triosephosphate isomerase
Arabidopsis thaliana AT3G55440   triosephosphate isomerase
Babesia bovis BBOV_II001220   triosephosphate isomerase protein, putative
Brugia malayi Bm1_29130   triosephosphate isomerase
Candida albicans CaO19.6745   similar to S. cerevisiae TPI1 (YDR050C) triose phosphate isomerase
Candida albicans CaO19.14037   similar to S. cerevisiae TPI1 (YDR050C) triose phosphate isomerase
Caenorhabditis elegans CELE_Y17G7B.7   Protein TPI-1
Cryptosporidium hominis Chro.10337   triose-phosphate isomerase
Cryptosporidium parvum cgd1_3040   triosephosphate isomerase
Chlamydia trachomatis CT_328   triosephosphate isomerase
Dictyostelium discoideum DDB_G0274471   triose phosphate isomerase
Drosophila melanogaster Dmel_CG2171   Triose phosphate isomerase
Escherichia coli b3919   triosephosphate isomerase
Echinococcus granulosus EgrG_000416400   triosephosphate isomerase
Entamoeba histolytica EHI_056480   triosephosphate isomerase
Echinococcus multilocularis EmuJ_000416400   triosephosphate isomerase
Giardia lamblia GL50803_93938   Triosephosphate isomerase, cytosolic
Homo sapiens ENSG00000111669   triosephosphate isomerase 1
Leishmania braziliensis LbrM.20.5360   triosephosphate isomerase
Leishmania donovani LdBPK_240870.1   triosephosphate isomerase
Leishmania infantum LinJ.24.0870   triosephosphate isomerase
Leishmania major LmjF.24.0850   triosephosphate isomerase
Leishmania mexicana LmxM.24.0850   triosephosphate isomerase
Loa Loa (eye worm) LOAG_09607   triosephosphate isomerase
Mycobacterium leprae ML0572   Probable triosephosphate isomerase Tpi (TIM)
Mus musculus ensembl-mmu:ENSMUSG00000023456   triosephosphate isomerase 1
Mycobacterium tuberculosis Rv1438   Probable triosephosphate isomerase Tpi (TIM)
Mycobacterium ulcerans MUL_1830   triosephosphate isomerase
Neospora caninum NCLIV_033270   hypothetical protein
Neospora caninum NCLIV_046900   hypothetical protein
Oryza sativa 4327400   Os01g0841600
Oryza sativa 4347691   Os09g0535000
Oryza sativa 4325211   Os01g0147900
Plasmodium berghei PBANKA_1303800   triosephosphate isomerase, putative
Plasmodium falciparum PF3D7_1439900   triosephosphate isomerase
Plasmodium knowlesi PKNH_1242400   triosephosphate isomerase, putative
Plasmodium vivax PVX_118495   triosephosphate isomerase, putative
Plasmodium yoelii PY04306   triosephosphate isomerase
Saccharomyces cerevisiae YDR050C   triose-phosphate isomerase TPI1
Schistosoma japonicum Sjp_0304690   ko:K01803 triosephosphate isomerase (TIM) [EC5.3.1.1], putative
Schistosoma mansoni Smp_003990   triosephosphate isomerase
Schmidtea mediterranea mk4.001789.01   Triosephosphate isomerase
Schmidtea mediterranea mk4.034460.04   Triosephosphate isomerase
Schmidtea mediterranea mk4.006707.00   Triosephosphate isomerase
Trypanosoma brucei gambiense Tbg972.11.6230   triosephosphate isomerase, putative
Trypanosoma brucei Tb927.11.5520   triosephosphate isomerase
Trypanosoma congolense TcIL3000.11.5810   triosephosphate isomerase, putative
Trypanosoma cruzi TcCLB.508647.200   triosephosphate isomerase, putative
Toxoplasma gondii TGME49_225930   triose-phosphate isomerase TPI-I
Toxoplasma gondii TGME49_233500   triose-phosphate isomerase TPI-II
Treponema pallidum TP0537   triosephosphate isomerase
Theileria parva TP04_0464   triosephosphate isomerase, putative
Trichomonas vaginalis TVAG_497370   triosephosphate isomerase, putative
Trichomonas vaginalis TVAG_096350   triosephosphate isomerase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0408   triosephosphate isomerase

Essentiality

LmjF.24.0850 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb11.02.3210 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb11.02.3210 Trypanosoma brucei significant loss of fitness in bloodstream forms (6 days) alsford
Tb11.02.3210 Trypanosoma brucei significant loss of fitness in procyclic forms alsford
Tb11.02.3210 Trypanosoma brucei significant loss of fitness in differentiation of procyclic to bloodstream forms alsford
b3919 Escherichia coli non-essential goodall
YDR050C Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1303800 Plasmodium berghei Essential plasmo
TGME49_233500 Toxoplasma gondii Probably essential sidik
TGME49_225930 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania mexicana 433604   557499   577907  
Annotator: aaronjr@u.washington.edu. Comment: chemical inhibition with TIM inhibitors leads to reduced enzyme activity in vitro; . References: 9654066
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania mexicana No drug identifiers listed for this gene.
Annotator: aaronjr@u.washington.edu. Comment: Drug: 53357-04-3. chemical inhibition with TIM inhibitors leads to reduced enzyme activity in vitro; . References: 16489748

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

  • Validation: inhibited in cell-free system
  • annotated by: aaronjr@u.washington.edu.
  • References: 16489748 9654066

Associated compounds / Druggability

Druggability index (range: 0 to 1): 0.8

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Oryctolagus cuniculus Triosephosphate isomerase Compounds References
Homo sapiens triosephosphate isomerase 1 Compounds References
Trypanosoma cruzi triosephosphate isomerase, putative 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
0.009 0.501 0
0.0091 0.4991 0
0.0303 1 0.5
0.0099 0.6314 0.6255
0.0097 0.6363 1
0.0313 1 1
0.0307 0.5446 1
0.01 0.2575 0.5522
0.0091 0.7857 1
0.011 0.2582 0
0.0091 0.7857 1
0.0091 0.7857 1

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Leishmania mexicana ( 2 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    LmjF.24.0850 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Leishmania mexicana ( 1 )

Bibliographic References

16 literature references were collected for this gene.

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Gene identifier LmjF.24.0850 (Leishmania major), triosephosphate isomerase
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