Detailed view for Rv0410c

Basic information

TDR Targets ID: 6799
Mycobacterium tuberculosis, Serine/threonine-protein kinase PknG (protein kinase G) (STPK G)
Source Database / ID:  Tuberculist 

pI: 5.5456 | Length (AA): 750 | MW (Da): 81577 | Paralog Number: 0

Signal peptide: N | GPI Anchor: | 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

PF00069   Protein kinase domain
PF16918   Protein kinase G tetratricopeptide repeat
PF16919   Protein kinase G rubredoxin domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0005524   ATP binding  
GO:0005515   protein binding  
GO:0005488   binding  
GO:0004713   protein tyrosine kinase activity  
GO:0004674   protein serine/threonine kinase activity  
GO:0004672   protein kinase activity  
GO:0006468   protein amino acid phosphorylation  

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
74 746 2pzi (A) 73 746 99.99 0 1 2.05543 -1.08
500 588 1hxi (A) 347 435 17.00 0 0.39 0.426667 -1.19

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
  • 2PZI:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Y0X:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4Y12:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. murphy
Show/Hide expression data references
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.

Orthologs

Ortholog group members (OG5_210922)

Species Accession Gene Product
Mycobacterium leprae ML0304   Probable serine-threonine protein kinase PknG (protein kinase G) (STPK G)
Mycobacterium tuberculosis Rv0410c   Serine/threonine-protein kinase PknG (protein kinase G) (STPK G)
Mycobacterium ulcerans MUL_2810   serine/threonine-protein kinase PknG

Essentiality

Rv0410c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
this record Mycobacterium tuberculosis essential nmpdr
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
growth (GO:0040007) decreased (PATO:0000468) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 15155913 15186418
growth (GO:0040007) decreased (PATO:0000468) inferred from animal model system (ECO:0000179) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 15186418
growth (GO:0040007) normal (PATO:0000461) inferred from in vitro culture assay (ECO:0000182) Mycobacterium tuberculosis No drug identifiers listed for this gene.
Annotator: crowther@u.washington.edu. Comment: 2007-12-31. References: 15155913

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): 0.4

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
Species Target Length Identity Alignment span Linked Drugs Reference
Plasmodium falciparum (isolate 3D7) Cell division control protein 2 homolog 288 aa 24.4% 283 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0067 0.5 0.5
0.0062 0.6935 0.5
0.0081 1 0.5
0.0007 0.5 0.5
0.0059 1 0.5
0.0007 0.5 0.5
0.0059 1 0.5
0.0088 0.4477 1
0.0063 0.7244 1
0.0092 1 0.5
0.0032 0.5 0.5
0.0033 0.5 0.5
0.0026 0.5 0.5
0.0061 0.6883 0.6563
0.0039 0.5 0.5
0.0066 0.3101 0.5
0.0003 0.5 0.5
0.0016 0.5 0.5
0.0007 0.5 0.5
0.0033 1 1
0.0018 0.5 0.5
0.0012 0.5 0.5
0.0098 0.3242 0.3676
0.0042 0.5 0.5
0.0016 0.5 0.5
0.0037 1 0.5
0.0063 1 1
0.0039 0.9485 1
0.0039 0.5 0.5
0.0032 0.5 0.5
0.0069 0.3067 1
0.0008 0.5 0.5
0.0091 1 0.5
0.0059 1 0.5
0.0012 0.5 0.5
0.0004 0.5 0.5
0.0023 0.5 0.5
0.0036 0.5 0.5
0.0012 0.5 0.5
0.0029 0.5 0.5
0.0022 0.5 0.5
0.0081 0.5 0.5
0.0056 1 0.5
0.0011 1 0.5
0.0027 1 0.5
0.0064 0.3377 0.5
0.0093 0.8828 0.5

Assayability

Assay information

  • Inhibition of Mycobacterium tuberculosis Protein kinase G by radiometric ATP consumptive assay ChEMBL
  • Inhibition of Mycobacterium tuberculosis Protein kinase G by radiometric ATP consumptive assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis PknG
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 100 uM by luciferase activity based ADP-Glo-luminescent kinase assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 12.5 uM by luciferase activity based ADP-Glo-luminescent kinase assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 50 uM by luciferase activity based ADP-Glo-luminescent kinase assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 25 uM by luciferase activity based ADP-Glo-luminescent kinase assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 6.25 uM by luciferase activity based ADP-Glo-luminescent kinase assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant PKnG expressed in Escherichia coli BL21 (DE3) cells using myelin basic protein substrate at 3.125 uM by luciferase activity based ADP-Glo-luminescent kinase assay

Reagent availability

No reagent availability information for this target.

Bibliographic References

81 literature references were collected for this gene.

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Gene identifier Rv0410c (Mycobacterium tuberculosis), Serine/threonine-protein kinase PknG (protein kinase G) (STPK G)
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