Detailed view for Rv2157c

Basic information

TDR Targets ID: 6552
Mycobacterium tuberculosis, Probable UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase MurF
Source Database / ID:  Tuberculist 

pI: 5.6406 | Length (AA): 510 | MW (Da): 51633 | 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

PF01225   Mur ligase family, catalytic domain
PF02875   Mur ligase family, glutamate ligase domain
PF08245   Mur ligase middle domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0071555   GO:cell wall organization  

GO:0047480   UDP-N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase activity  
GO:0005737   cytoplasm  
GO:0016874   ligase activity  
GO:0005524   ATP binding  
GO:0051301   cell division  
GO:0009273   peptidoglycan-based cell wall biogenesis  
GO:0009252   peptidoglycan biosynthetic process  
GO:0009058   biosynthetic process  
GO:0008360   regulation of cell shape  

Structural information

Modbase 3D models:

There are 4 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
1 500 4qdi (A) 11 463 31.00 0 1 1.20009 0.56
2 424 3zm6 (A) 1 384 36.00 0 1 1.13771 0.31
3 499 4cvk (A) 9 450 38.00 0 1 1.21381 0.5
132 336 5vvw (A) 118 315 29.00 0.000089 1 0.723261 -0.12

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

Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Dormant phase. murphy
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Dormant phase. hasan
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_132578)

Species Accession Gene Product
Chlamydia trachomatis CT_756   UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminoligase
Escherichia coli b0086   UDP-N-acetylmuramoyl-tripeptide:D-alanyl-D-alanine ligase
Mycobacterium leprae ML0910   ProbableUDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase MurF
Mycobacterium tuberculosis Rv2157c   Probable UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase MurF
Mycobacterium ulcerans MUL_3505   UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase MurF
Schmidtea mediterranea mk4.041360.01  
Schmidtea mediterranea mk4.065125.02  
Treponema pallidum TP0386   UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate--D-alanyl-D-alanine ligase (murF)
Wolbachia endosymbiont of Brugia malayi Wbm0238   UDP-N-acetylmuramyl pentapeptide synthase

Essentiality

Rv2157c has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu2190 this record Mycobacterium tuberculosis essential nmpdr
b0086 Escherichia coli essential goodall
Show/Hide essentiality data references
  • 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
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan

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

Druggability index (range: 0 to 1): 0.3

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
Staphylococcus epidermidis (strain ATCC 35984 / RP62A) UDP-N-acetylmuramoyl-tripeptide--D-alanyl-D-alanine ligase Compounds References
Streptococcus pneumoniae R6 UDP-N-acetylmuramoylalanine-D-glutamyl-lysine-D-alanyl-D-alanine ligase 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
0.1764 0.4456 0.4465
0.0258 0.4556 0.4248
0.1079 0.2707 0.2681
0.1479 0.389 0.3884
0.6655 1 1
0.1864 0.5809 1
0.167 0.3542 0.3539
0.6504 1 1
0.0603 0.8047 1
0.6706 1 1
0.0603 0.8111 1
0.1079 0.2707 0.2681
0.4284 1 1
0.0325 0.5809 1
0.5672 0.3401 1
0.1764 0.4456 0.4465
0.6589 1 1
0.5648 1 1
0.0526 1 1
0.0603 1 0.5
0.1764 0.4456 0.4465
0.0316 0.3937 0.4248
0.1764 0.4456 0.4465
0.6964 1 1
0.6372 1 1
0.6497 1 1
0.2435 0.3238 0.6044
0.6762 1 1
0.1079 0.2707 0.2681
0.1764 0.4456 0.4465
0.0818 0.3696 0.3677
0.03 0.4343 0.4258
0.1247 1 1
0.1079 0.2707 0.2681
0.2435 0.3238 0.6044
0.5612 1 1
0.0325 1 1
0.704 1 1
0.6151 1 1
0.6751 1 1
0.1764 0.4456 0.4465
0.6762 1 1
0.555 1 1
0.1728 0.8648 1
0.6463 1 1
0.1326 0.8755 1
0.1635 0.4001 0.3631
0.0555 0.3244 1
0.0316 0.4199 0.4624
0.2435 0.3238 0.6044
0.1764 0.4456 0.4465
0.1844 1 1
0.6812 1 1
0.6561 1 1
0.0278 0.3292 0.4829
0.0603 0.8047 1
0.0798 0.9782 1
0.1403 1 1
0.6372 1 1
0.0603 0.8111 1
0.1108 0.3139 0.2685
0.1079 0.2707 0.2681
0.0288 0.2661 0.3942
0.0526 1 1
0.1638 0.2817 0.2407
0.0644 0.3679 0.3459
0.2412 1 1
0.1764 0.4456 0.4465
0.0603 0.8047 1
0.0803 0.3574 0.3316
0.3216 1 1
0.7104 1 1
0.5612 1 1
0.669 1 1
0.5672 0.4088 1
0.6104 1 1
0.0219 0.3695 1
0.0325 1 1
0.0603 0.8047 1
0.555 1 1
0.462 1 1
0.0325 0.5798 1
0.1079 0.2707 0.2681
0.6783 1 1
0.0474 0.4009 0.4009
0.4012 0.3342 1
0.1764 0.4456 0.4465
0.1079 0.2707 0.2681
0.1221 0.3729 0.3725
0.667 1 1
0.1792 1 1
0.555 1 1
0.1079 0.2707 0.2681
0.1506 0.3223 0.3223
0.606 1 1
0.1469 0.3635 0.3037
0.1638 0.2817 0.2407
0.2435 0.3238 0.6044
0.1764 0.4456 0.4465
0.167 0.3542 0.3539
0.6751 1 1
0.3843 1 1
0.1112 1 1
0.5877 1 1
0.0818 0.367 0.3533
0.2214 0.9193 1
0.1764 0.4456 0.4465
0.0325 1 1
0.0261 0.3097 1
0.6144 1 1
0.2397 0.3663 0.3659
0.1764 0.4456 0.4465
0.1561 0.3439 0.3439
0.092 0.2931 0.2931
0.6682 1 1
0.7069 1 1
0.0288 0.2661 0.3942
0.6497 1 1
0.1426 0.3157 0.3095
0.1638 0.2817 0.2407
0.0258 0.4556 0.4248
0.6131 1 1
0.2118 0.3078 1
0.6589 1 1
0.1145 0.3602 0.3602
0.1079 0.2707 0.2681
0.1764 0.4456 0.4465
0.0803 0.3607 0.3316
0.1605 0.2855 0.2855
0.0614 1 1
0.0603 0.8047 1
0.5612 1 1
0.1764 0.4456 0.4465
0.1764 0.4456 0.4465
0.6069 1 1
0.6504 1 1
0.0188 0.4197 0.8481
0.6144 1 1
0.0692 0.279 0.244
0.0611 1 1
0.6706 1 1
0.1764 0.4456 0.4465
0.6682 1 1
0.1676 0.3493 0.3266
0.2412 1 1
0.704 1 1
0.663 1 1
0.6689 1 1
0.0325 0.8981 1
0.1506 0.3223 0.3223
0.0316 0.3246 0.4816
0.5672 0.4088 1
0.1326 0.8755 1
0.1561 0.3439 0.3439
0.1221 0.3729 0.3725
0.0483 0.4057 0.4057
0.2397 0.3663 0.3659
0.5672 0.3401 1
0.5681 1 1
0.2169 1 1
0.2666 1 1
0.6463 1 1
0.2397 0.3663 0.3659
0.3219 1 1
0.0672 0.5008 0.5193
0.6751 1 1
0.1079 0.2707 0.2681
0.2155 1 1
0.1638 0.2817 0.2407
0.1676 0.3493 0.3266
0.7069 1 1
0.6504 1 1
0.0603 0.8047 1
0.6504 1 1
0.1079 0.2707 0.2681
0.3872 0.2976 1
0.4033 1 1
0.6751 1 1
0.0288 0.2661 0.3942
0.6783 1 1
0.1638 0.2817 0.2407
0.6751 1 1
0.1182 0.3652 0.3652
0.6672 1 1
0.6751 1 1
0.6139 1 1
0.6627 1 1
0.167 0.3542 0.3539
0.1479 0.389 0.3884
0.1526 1 1
0.1075 0.3764 0.3361
0.2397 0.3663 0.3659

Assayability

Assay information

No assay information for this target.

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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Gene identifier Rv2157c (Mycobacterium tuberculosis), Probable UDP-N-acetylmuramoylalanyl-D-glutamyl-2,6-diaminopimelate-D-alanyl-D-alanyl ligase MurF
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