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 / Rv0410c 

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

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

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:0004672   protein kinase activity  
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: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:

  • 2PZI: Crystal Structure of Protein kinase PknG from Mycobacterium tuberculosis in Complex with Tetrahydrobenzothiophene AX20017
  • Honnappa, S., Steinmetz, M.O.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    2.40 X-RAY DIFFRACTION 10050 1362 2007-05-18 2007-07-24 2017-10-18
  • Ligand information
  • 2-[(CYCLOPROPYLCARBONYL)AMINO]-4,5,6,7-TETRAHYDRO-1-BENZOTHIOPHENE-3-CARBOXAMIDE C1CCc2c(c(c(s2)NC(=O)C3CC3)C(=O)N)C1 non-polymer Search in DB
  • CADMIUM ION [Cd+2] non-polymer Search in DB
  • CHLORIDE ION [Cl-] non-polymer Search in DB
  • GLYCEROL C(C(CO)O)O non-polymer Search in DB
  • 4Y0X: Crystal structure of the S/T protein kinase PknG from Mycobacterium tuberculosis in complex with ADP
  • Lisa, M.N., Alzari, P.M.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    1.74 X-RAY DIFFRACTION 2459 375 2015-02-06 2015-05-20 2015-06-10
  • Ligand information
  • ADENOSINE-5'-DIPHOSPHATE c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)CO[P@](=O)(O)OP(=O)(O)O)O)O)N non-polymer Search in DB
  • MAGNESIUM ION [Mg+2] non-polymer Search in DB
  • ZINC ION [Zn+2] non-polymer Search in DB
  • 4Y12: Crystal structure of the S/T protein kinase PknG from Mycobacterium tuberculosis in complex with AGS
  • Lisa, M.N., Alzari, P.M.
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
    1.90 X-RAY DIFFRACTION 2413 375 2015-02-06 2015-05-20 2015-06-10
  • Ligand information
  • PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER c1nc(c2c(n1)n(cn2)[C@H]3[C@@H]([C@@H]([C@H](O3)COP(=O)(O)OP(=O)(O)OP(=S)(O)O)O)O)N non-polymer Search in DB
  • MAGNESIUM ION [Mg+2] non-polymer Search in DB
  • ZINC ION [Zn+2] non-polymer Search in DB

Expression

Upregulation Percent Ranking Shows this level of upregulation in
This gene ranks in the upper 60-80% group of genes. Dormant phase.
Upregulation Percent Ranking Shows this level of upregulation in
This gene ranks in the lower 20-40% group of genes. Dormant phase.
Show/Hide expression data references
  • murphy Identification of gene targets against dormant phase Mycobacterium tuberculosis infections.
  • hasan Prioritizing genomic drug targets in pathogens: application to Mycobacterium tuberculosis.

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 this record   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
  • 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.
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84

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 log in using your TDR Targets username and password and send them to us using the corresponding form in this page (only visible to registered users) or 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
0.0063 0.7244 1
0.0061 0.6883 0.6563

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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