Detailed view for Rv2981c

Basic information

TDR Targets ID: 981553
Mycobacterium tuberculosis, Probable D-alanine--D-alanine ligase DdlA (D-alanylalanine synthetase) (D-ala-D-ala ligase)

Source Database / ID:  Tuberculist 

pI: 5.1376 | Length (AA): 373 | MW (Da): 39678 | Paralog Number: 0

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

Druggability Group : DG1

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

No Pfam domain information for this protein.

Gene Ontology

Mouse over links to read term descriptions.
No GO information for this protein.

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
10 373 3lwb (B) 10 373 99.99 0 1 1.84607 0.03
65 169 5dmx (E) 11 117 40.00 0.0000000005 0.57 0.724701 -0.03

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:

No structure availble in the PDB for this protein

Expression

No expression data available for this gene

Orthologs

Ortholog group members (OG5_130117)

Species Accession Gene Product
Arabidopsis thaliana AT3G08840   D-alanine--D-alanine ligase family protein
Escherichia coli b0381   D-alanine-D-alanine ligase A
Escherichia coli b0092   D-alanine:D-alanine ligase
Mycobacterium leprae ML1678c   PROBABLE D-ALANINE--D-ALANINE LIGASE DDLA (D-ALANYLALANINE SYNTHETASE) (D-ALA-D-ALA LIGASE)
Mycobacterium tuberculosis Rv2981c   Probable D-alanine--D-alanine ligase DdlA (D-alanylalanine synthetase) (D-ala-D-ala ligase)
Mycobacterium ulcerans MUL_1976   D-alanyl-alanine synthetase A
Oryza sativa 4344370   Os07g0691200
Treponema pallidum TP0670   D-alanyl-alanine synthetase A
Wolbachia endosymbiont of Brugia malayi Wbm0570   D-alanine--D-alanine ligase

Essentiality

Rv2981c has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b0092 Escherichia coli non-essential goodall
b0381 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • 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.
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • 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.

Phenotypes and Validation (curated)

We have no manually annotated phenotypes for this target. What does this mean? / Care to help?

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

Known modulators for this target

No chemical compounds associated to this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Escherichia coli D-alanine:D-alanine ligase Compounds References
Helicobacter pylori (strain HPAG1) D-alanine--D-alanine ligase Compounds References
By sequence similarity to non orthologous druggable targets
No additional associated druggable targets

Obtained from network model

Ranking Plot

No enough druggable targets predicted through repurposing network model to make a plot

Putative Drugs List


Compound Raw Global Species
0.0372 0.2619 0.6583

Assayability

Assay information

  • ChEMBL
  • Competitive inhibition of D-alanine-D-alanine ligase in Mycobacterium tuberculosis H37Rv at MIC preincubated for 16 hrs followed by D-Ala-[2H] addition measured over 8 hrs by LC-MS/MS analysis
  • ChEMBL
  • Inhibition of D-alanine-D-alanine ligase in Mycobacterium tuberculosis H37Rv assessed as inhibition of denovo D-Alanyl-D-alanine synthesis at 2 times MIC preincubated for 16 hrs followed L-Ala-[13C]-[3H] addition measured over 8 hrs by LC-MS/MS analysis
  • ChEMBL
  • Inhibition of D-alanine-D-alanine ligase in Mycobacterium tuberculosis H37Rv assessed as inhibition of denovo D-Alanyl-D-alanine synthesis at MIC preincubated for 16 hrs followed by L-Ala-[13C]-[3H] addition measured over 8 hrs by LC-MS/MS analysis
  • ChEMBL
  • Inhibition of D-alanine-D-alanine ligase in Mycobacterium tuberculosis H37Rv assessed as depletion in D-Alanyl-D-alanine level preincubated for 16 hrs measured post 24 hrs of compound washout

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

If you have references for this gene, please enter them in a user comment (below) or Contact us.

User comments

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Gene identifier Rv2981c (Mycobacterium tuberculosis), Probable D-alanine--D-alanine ligase DdlA (D-alanylalanine synthetase) (D-ala-D-ala ligase)
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