Detailed view for LmjF.35.3010

Basic information

TDR Targets ID: 26522
Leishmania major, glyoxalase I,trypanothione-dependent glyoxalase I
Source Database / ID:  TriTrypDB  GeneDB

pI: 4.5591 | Length (AA): 141 | MW (Da): 16319 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | 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

PF00903   Glyoxalase/Bleomycin resistance protein/Dioxygenase superfamily

Gene Ontology

Mouse over links to read term descriptions.
GO:0046872   metal ion binding  
GO:0004462   lactoylglutathione lyase activity  

Metabolic Pathways

Pyruvate metabolism (KEGG)

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
3 141 2c21 (A) 3 141 99.99 0 1 2.24 -1.64
3 141 2c21 (A) 3 141 99.99 0 1 2.20682 -1.27

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
  • 2C21:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile amastigotes. Fernandes MC
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile 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_127627)

Species Accession Gene Product
Arabidopsis thaliana AT1G08110   lactoylglutathione lyase
Brugia malayi Bm1_18670   lactoylglutathione lyase
Candida albicans CaO19.6058   glyoxalase I
Candida albicans CaO19.13479   glyoxalase I
Dictyostelium discoideum DDB_G0291265   glyoxylase I
Drosophila melanogaster Dmel_CG1707   CG1707 gene product from transcript CG1707-RA
Escherichia coli b1651   glyoxalase I, Ni-dependent
Homo sapiens ENSG00000124767   glyoxalase I
Leishmania braziliensis LbrM.34.2920   glyoxalase I
Leishmania donovani LdBPK_353060.1   glyoxalase I
Leishmania infantum LinJ.35.3060   glyoxalase I,trypanothione-dependent glyoxalase I
Leishmania major LmjF.35.3010   glyoxalase I,trypanothione-dependent glyoxalase I
Leishmania mexicana LmxM.34.3010   glyoxalase I,trypanothione-dependent glyoxalase I
Loa Loa (eye worm) LOAG_03565   hypothetical protein
Mus musculus ENSMUSG00000024026   glyoxalase 1
Neospora caninum NCLIV_064370   Lactoylglutathione lyase (EC 4.4.1.5), related
Oryza sativa 4338324   Os05g0295800
Onchocerca volvulus OVOC11536   Lactoylglutathione lyase homolog
Plasmodium berghei PBANKA_0933900   glyoxalase I, putative
Plasmodium falciparum PF3D7_1113700   glyoxalase I
Plasmodium knowlesi PKNH_0911300   glyoxalase I, putative
Plasmodium vivax PVX_091330   glyoxalase I, putative
Plasmodium yoelii PY00733   lactoylglutathione lyase, putative
Saccharomyces cerevisiae YML004C   lactoylglutathione lyase GLO1
Trypanosoma cruzi TcCLB.510743.70   lactoylglutathione lyase-like protein, putative
Trypanosoma cruzi TcCLB.510659.240   lactoylglutathione lyase-like protein, putative
Toxoplasma gondii TGME49_248400   glyoxalase I, putative

Essentiality

LmjF.35.3010 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b1651 Escherichia coli non-essential goodall
PBANKA_0933900 Plasmodium berghei Dispensable plasmo
TGME49_248400 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • 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
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection

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 donovani 103413   415029  
Annotator: crowther@u.washington.edu. Comment: Drug: 85261-23-0; Drug: 104951-62-4; Drug: 204446-06-0; Drug: 277310-54-0; Drug: 277310-55-1; Drug: 277310-56-2; Drug: 277310-57-3; Drug: 277310-58-4; Drug: 277310-59-5; Drug: 277310-60-8; Drug: 277310-61-9; Drug: 33812-60-1; Drug: 104928-26-9; Drug: 104928-27-0; Drug: 104928-28-1; Drug: 104928-29-2; Drug: 104951-63-5; Drug: 204445-92-1; Drug: 204445-99-8; Drug: 277310-53-9 . some chemical inhibitors reduced glyoxalase activity. References: 10821719
growth (GO:0040007) normal (PATO:0000461) single cell organism (CARO:0000064) inferred from in-silico analysis (ECO:0000043) Leishmania infantum No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: computer modeling suggests that GLO1 and GLO2 are not good targets because their activities don't greatly affect methylglyoxal concentration. References: 15885089
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Leishmania major 103413   307979   415029   555923  
Annotator: crowther@u.washington.edu. Comment: Drug: 886970-70-3; Drug: 886970-71-4 . chemical inhibitors selectively reduce Leishmania but not human GLO1 activity (or vice versa). References: 16430697

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): 0.6

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
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
Homo sapiens glyoxalase I Compounds References
Plasmodium falciparum glyoxalase I Compounds References
Saccharomyces cerevisiae lactoylglutathione lyase GLO1 Compounds References
Trypanosoma cruzi lactoylglutathione lyase-like protein, 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
0.0775 0.9315 1
0.1251 0.7189 1
0.1323 0.5949 1
0.0232 0.2903 1
0.0465 0.4779 0.9751
0.1452 1 1
0.1581 0.3867 1
0.108 1 1
0.0966127 1 1
0.0835 0.3161 0.987
0.108 1 1
0.1251 0.7189 1
0.1295 1 1
0.0602 0.7403 1
0.1349 0.5571 1
0.2991 1 1
0.0835 0.3161 0.987
0.0251 0.4658 1
0.0382 0.4516 1
0.1581 0.3867 1
0.0443 1 1
0.1071 1 1
0.08 0.356 1
0.0232 1 1
0.1306 1 0.5
0.139721 1 0.5
0.0443 1 1
0.2991 1 1
0.1179 1 1
0.1046 1 1
0.0393 0.2815 1
0.1059 1 0.5
0.1573 1 1
0.1283 1 1
0.0835 1 1
0.0111 0.2716 0.4766
0.0761 1 1
0.108 1 1
0.038 0.2886 0.7562
0.0654 0.367 1
0.0198 0.3331 0.7598
0.1426 1 1
0.0358 0.2883 0.7569
0.0194 0.3716 0.5
0.0755 1 1
0.0761 1 1
0.0186 0.5889 0.5
0.0929 0.4041 1
0.1334 1 1
0.0205 1 1
0.0354 1 0.5
0.0198 0.6479 1
0.0622 0.2734 1
0.1294 0.2596 1
0.0402 0.4871 1
0.02 0.392 0.5
0.1323 0.5949 1
0.1055 1 1
0.0835 0.3161 0.987
0.0399 0.7908 0.5
0.0844 0.3778 1
0.1583 1 1
0.108 1 1
0.108 1 1
0.0405 0.2786 0.4342
0.0391 0.4757 1
0.0595 0.4345 1
0.0403 0.991 1
0.1148 0.5577 1
0.2671 1 1
0.0188 0.3141 1
0.019 0.4043 0.7687
0.0929 0.7062 1
0.0187 0.4339 1
0.0629 0.8426 1
0.0829 1 1
0.0378 0.432 1
0.1323 0.5949 1
0.0605 0.3168 0.3601
0.0806 1 1
0.1202 1 1
0.0431 0.5 0.5
0.1251 0.7189 1
0.1277 1 1
0.0801 0.3037 1
0.0189 0.3189 0.9029
0.0232 0.29 0.2898
0.1306 1 0.5
0.0945 1 1
0.0232 1 1
0.0196 1 1
0.1574 1 1
0.0221 1 0.5
0.1055 1 1
0.0596 1 1
0.2907 1 1
0.2261 0.8461 0.8663
0.0813 1 1
0.0384 0.8718 1
0.1323 0.5949 1
0.0929 0.7062 1
0.0232 1 1
0.0232 1 1
0.0384846 1 1
0.0199 0.6479 1
0.3063 1 1
0.1334 1 1
0.0189 1 0.5
0.1403 1 1
0.0751 1 1
0.0379 0.5 0.5
0.0835 0.3161 0.987
0.0196 0.4171 0.7447
0.0232 0.4317 1
0.1349 0.5571 1
0.108 1 1
0.2541 1 1
0.0775 0.9315 1
0.0991 1 1
0.0443 1 1
0.3128 1 1
0.0605 0.3168 0.3601
0.0203 0.648 1
0.1264 1 1
0.0835 0.3161 0.987
0.0232 1 1
0.0386 0.5416 1
0.137 0.5579 1
0.2991 1 1
0.1403 1 1
0.0813 1 1
0.108 1 1
0.1323 1 0.5
0.0561 0.3039 1
0.0788 1 1
0.133 0.3224 1
0.1294 0.2596 1
0.0196 0.3529 0.5
0.1294 0.2596 1
0.0835 0.3161 0.987
0.0835 0.3161 0.987
0.1337 0.5454 0.5453
0.0952 1 1
0.0602 0.7403 1
0.0992 1 1
0.0374 0.3862 1
0.1088 1 1
0.0465 0.4779 0.9751
0.0801 0.3037 1
0.0232 1 1
0.0582 0.6925 1
0.0465 0.5 0.5
0.0216 0.2524 1
0.0843 0.2609 1
0.0796 0.3036 1
0.0186 0.271 1
0.0814 1 1
0.1292 0.8444 1
0.0358 0.2883 0.7569
0.0605 0.3168 0.3601
0.019 0.6467 0.6414
0.0403 0.991 1
0.0291 1 1
0.0788 1 1
0.0787 0.9548 1
0.0629 0.8426 1
0.1585 1 1
0.1333 1 1
0.1071 1 1
0.1592 1 1
0.0186 0.5889 0.5
0.0603 1 1
0.0232 0.7063 0.5
0.0431 1 0.5
0.2445 1 1
0.069 0.9317 1
0.1213 1 1
0.0378 1 1
0.1139 1 0.5
0.1028 1 1
0.0818 1 1
0.2991 1 1
0.0208 1 1
0.0465 0.5 0.5
0.1377 0.3339 1
0.0838 1 1
0.0929 0.7062 1
0.0218 1 1
0.0997 1 1
0.0385 0.5491 1
0.1581 0.3867 1
0.0405 0.2786 0.4342
0.0198 0.7702 0.759
0.108 1 1
0.2657 1 1
0.0232 0.8164 1
0.0465 0.4779 0.9751
0.1365 1 1
0.1292 0.8444 1
0.0602 0.7403 1
0.0985 1 1
0.0577 1 1
0.0806 1 1
0.1459 1 1
0.0779 1 1
0.106 1 0.5
0.0612 0.3486 1
0.0393 0.3045 1
0.0187 0.7073 0
0.1334 1 1
0.133 0.3224 1
0.0992 1 1
0.1251 0.7189 1
0.0774 1 1
0.0187 0.5857 1
0.0465 0.4779 0.9751
0.1037 1 1
0.0187 0.646 1
0.0384 0.8718 1
0.1581 0.3867 1
0.0755 1 1
0.0387 0.4194 1
0.0384846 1 1
0.0187 0.5857 1
0.0629 0.8426 1
0.039 1 1
0.0966 0.3695 1
0.082 0.7919 1
0.0966 0.3695 1

Assayability

Assay information

  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Leishmania donovani ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    LmjF.35.3010 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Leishmania major ( 2 )

Bibliographic References

No literature references available for this target.

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Gene identifier LmjF.35.3010 (Leishmania major), glyoxalase I,trypanothione-dependent glyoxalase I
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