Detailed view for LmjF.12.0220

Basic information

TDR Targets ID: 27550
Leishmania major, hydroxyacylglutathione hydrolase, putative,glyoxalase II, putative
Source Database / ID:  TriTrypDB  GeneDB

pI: 6.4965 | Length (AA): 295 | MW (Da): 32561 | 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

PF00753   Metallo-beta-lactamase superfamily
PF16123   Hydroxyacylglutathione hydrolase C-terminus

Gene Ontology

Mouse over links to read term descriptions.
GO:0016787   hydrolase activity  

Metabolic Pathways

Pyruvate metabolism (KEGG)

Structural information

Modbase 3D models:

There are 3 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
13 295 1qh5 (A) 1 253 36.00 0 1 1.42 -1.22
13 295 1xm8 (A) 1 252 31.00 0 1 1.26 -1.41
1 293 2p18 (A) 1 293 97.00 0 1 2.21612 -1.91

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
  • 2P18:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 2P1E:
  • 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_127291)

Species Accession Gene Product
Arabidopsis thaliana AT2G31350   Hydroxyacylglutathione hydrolase 2
Arabidopsis thaliana AT2G43430   glyoxalase 2-1
Arabidopsis thaliana AT1G06130   glyoxalase 2-4
Arabidopsis thaliana AT3G10850   hydroxyacylglutathione hydrolase
Babesia bovis BBOV_IV004560   hydroxyacylglutathione hydrolase, putative
Brugia malayi Bm1_40000   Chain A, Human Glyoxalase Ii With Cacodylate And Acetate Ions Present In The Active Site.
Candida albicans CaO19.4088   glyoxylase 2
Candida albicans CaO19.11569   glyoxylase 2
Caenorhabditis elegans CELE_Y17G7B.3   Protein Y17G7B.3
Dictyostelium discoideum DDB_G0285717   beta-lactamase domain-containing protein
Drosophila melanogaster Dmel_CG4365   CG4365 gene product from transcript CG4365-RB
Escherichia coli b0212   hydroxyacylglutathione hydrolase
Echinococcus granulosus EgrG_000704000   hydroxyacylglutathione hydrolase
Echinococcus multilocularis EmuJ_000704000   hydroxyacylglutathione hydrolase
Homo sapiens 3029   hydroxyacylglutathione hydrolase
Leishmania braziliensis LbrM.12.0240   hydroxyacylglutathione hydrolase, putative,glyoxalase II, putative
Leishmania donovani LdBPK_120200.1   glyoxalase II, putative
Leishmania infantum LinJ.12.0200   glyoxalase II, putative
Leishmania major LmjF.12.0220   hydroxyacylglutathione hydrolase, putative,glyoxalase II, putative
Leishmania mexicana LmxM.12.0220   hydroxyacylglutathione hydrolase, putative,glyoxalase II, putative
Loa Loa (eye worm) LOAG_02231   hydroxyacylglutathione hydrolase
Mycobacterium leprae ML1912   POSSIBLE GLYOXALASE II (HYDROXYACYLGLUTATHIONE HYDROLASE) (GLX II)
Mus musculus ENSMUSG00000024158   hydroxyacyl glutathione hydrolase
Mycobacterium tuberculosis Rv0634c   Possible glyoxalase II (hydroxyacylglutathione hydrolase) (GLX II)
Mycobacterium ulcerans MUL_0715   glyoxalase II, GloB
Neospora caninum NCLIV_023550   hydroxyacylglutathione hydrolase, putative
Oryza sativa 4347581   Os09g0516600
Oryza sativa 4332736   Os03g0332400
Onchocerca volvulus OVOC5133   Hydroxyacylglutathione hydrolase, mitochondrial homolog
Plasmodium berghei PBANKA_1004000   cytosolic glyoxalase II, putative
Plasmodium falciparum PF3D7_0406400   cytosolic glyoxalase II
Plasmodium knowlesi PKNH_0304400   cytosolic glyoxalase II, putative
Plasmodium vivax PVX_000925   hydroxyacyl glutathione hydrolase, putative
Plasmodium yoelii PY05100   hypothetical protein
Saccharomyces cerevisiae YOR040W   hydroxyacylglutathione hydrolase GLO4
Saccharomyces cerevisiae YDR272W   hydroxyacylglutathione hydrolase GLO2
Schistosoma japonicum Sjp_0078530   ko:K01069 hydroxyacylglutathione hydrolase [EC3.1.2.6], putative
Schistosoma mansoni Smp_091010   hydroxyacylglutathione hydrolase (Glyoxalase II) (Glx II)
Schmidtea mediterranea mk4.000398.04   Hydroxyacylglutathione hydrolase, mitochondrial
Schmidtea mediterranea mk4.058797.00   Hydroxyacylglutathione hydrolase, mitochondrial
Schmidtea mediterranea mk4.000945.09   Hydroxyacylglutathione hydrolase, mitochondrial
Trypanosoma brucei gambiense Tbg972.6.780   hydroxyacylglutathione hydrolase, putative,glyoxalase II
Trypanosoma brucei Tb927.6.1080   hydroxyacylglutathione hydrolase, putative
Trypanosoma congolense TcIL3000_6_540   hydroxyacylglutathione hydrolase, putative
Trypanosoma cruzi TcCLB.509429.290   hydroxyacylglutathione hydrolase, putative
Trypanosoma cruzi TcCLB.507603.230   hydroxyacylglutathione hydrolase, putative
Toxoplasma gondii TGME49_281630   hydroxyacylglutathione hydrolase
Theileria parva TP01_0292   hydroxyacyl glutathione hydrolase, putative
Trichomonas vaginalis TVAG_243530   beta lactamase domain, putative

Essentiality

LmjF.12.0220 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
Tb927.6.1080 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (3 days) alsford
Tb927.6.1080 Trypanosoma brucei no significant loss or gain of fitness in bloodstream forms (6 days) alsford
Tb927.6.1080 Trypanosoma brucei no significant loss or gain of fitness in procyclic forms alsford
Tb927.6.1080 Trypanosoma brucei no significant loss or gain of fitness in differentiation of procyclic to bloodstream forms alsford
b0212 Escherichia coli non-essential goodall
TGME49_281630 Toxoplasma gondii Essentiality uncertain sidik
Show/Hide essentiality data references
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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

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

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Bos taurus Hydroxyacylglutathione hydrolase, mitochondrial Compounds References
Homo sapiens hydroxyacylglutathione hydrolase Compounds References
Rattus norvegicus Glyoxalase II 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
0.0065 0.5 0.5
0.0098 0.5 0.5
0.0282 0.3876 1
0.0101 0.5 0.5
0.0139 0.3313 1
0.0099 0.253 0
0.0138 0.8072 0.8072
0.0259 0.336 1
0.0033 0.5 0.5
0.0153 1 0.5
0.0252 0.2685 1
0.0051 0.5023 0.5
0.0068 0.616 0.5
0.0134 0.3422 1
0.0161 1 1
0.0263 0.5703 1
0.0085 0.271 1
0.0284 0.6112 1
0.0208 0.4509 1
0.0304 0.3722 1
0.0153 1 0.5
0.0179 1 0.5
0.0183 1 1
0.0269 1 1
0.0224 1 1
0.0099 1 0.5
0.032 0.4025 1
0.0099 1 0.5
0.0333 0.487 1
0.0181 1 1
0.0088 0.4106 0.5
0.0252 0.2685 1
0.0031 0.5 0.5
0.0156 1 1
0.0215 0.5175 0.5
0.0252 0.2685 1
0.0141 0.5 0.5
0.03 0.9089 1
0.0307 0.4131 1
0.024 0.347 1
0.03 0.9089 1
0.0173 0.5058 1
0.035 0.2506 1
0.0115 1 0.5
0.0249 0.3365 1
0.0404 0.2792 1
0.0101 0.5 0.5
0.0019 0.5 0.5
0.0286 1 0.5
0.0304 0.3722 1
0.0367 0.531 1
0.0151 0.5 0.5
0.0079 0.301 0.5

Assayability

Assay information

  • Assay for Glyoxalase II (3.1.2.6 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Leishmania infantum ( 1 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    LmjF.12.0220 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Leishmania donovani ( 1 )

Bibliographic References

5 literature references were collected for this gene.

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Gene identifier LmjF.12.0220 (Leishmania major), hydroxyacylglutathione hydrolase, putative,glyoxalase II, putative
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