Detailed view for Rv1170

Basic information

TDR Targets ID: 6538
Mycobacterium tuberculosis, N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB (GlcNAc-Ins deacetylase)
Source Database / ID:  Tuberculist 

pI: 5.1248 | Length (AA): 303 | MW (Da): 31742 | 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

PF02585   GlcNAc-PI de-N-acetylase

Gene Ontology

Mouse over links to read term descriptions.
GO:0035595   GO:N-acetylglucosaminylinositol deacetylase activity  

Metabolic Pathways

This gene is not mapped to any metabolic pathway in KEGG.

Structural information

Modbase 3D models:

There is 1 model calculated for this protein. More info on this model, including the model itself is available at: Modbase

Target Beg Target End Template Template Beg Template End Identity Evalue Model Score MPQS zDope
1 303 1q7t (A) 1 303 99.99 0 1 2.1754 -1.06

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
  • 1Q74:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 1Q7T:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4EWL:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile Dormant phase. murphy
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_174832)

Species Accession Gene Product
Mycobacterium leprae ML1495c   N-Acetyl-1-D-myo-Inosityl-2-Amino-2-Deoxy-alpha-D-Glucopyranoside Deacetylase MshB (GlcNAc-Ins deacetylase)
Mycobacterium tuberculosis Rv1170   N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB (GlcNAc-Ins deacetylase)
Mycobacterium ulcerans MUL_1017   N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB

Essentiality

Rv1170 has direct evidence of essentiality
Gene/Ortholog Organism Phenotype Source Study
mtu1191 this record Mycobacterium tuberculosis non-essential nmpdr
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.
  • 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.
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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.
  • 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
  • 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
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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
response to drug (GO:0042493) increased sensitivity toward (PATO:0001549) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium tuberculosis 540786   540787   540788   583761  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 11092856 12622824
response to oxidative stress (GO:0006979) increased sensitivity toward (PATO:0001549) inferred from loss-of-function mutant phenotype (ECO:0000016) Mycobacterium tuberculosis 205696  
Annotator: crowther@u.washington.edu. Comment: 2007-12-26. References: 11092856
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: 2007-12-26. References: 11092856 12622824

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): 0.2

Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium leprae N-Acetyl-1-D-myo-Inosityl-2-Amino-2-Deoxy-alpha-D-Glucopyranoside Deacetylase MshB (GlcNAc-Ins deacetylase) 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
0.1559 0.2818 0.6028
0.3359 0.6037 0.6023
0.2687 1 1
0.6317 0.6043 0.5995
0.2225 1 1
0.3134 0.6039 0.5995
0.6022 0.6039 0.5995
0.1952 0.5872 0.5872
0.5947 0.604 0.6029
0.1192 0.4514 0.6028
0.1445 0.2737 0.6026
0.1608 0.4865 1
0.127 0.3307 0.616
0.6368 0.6039 0.6039
0.3359 0.6037 0.6023
0.6463 0.604 0.604
0.3359 0.7776 1
0.6371 0.6039 0.5995
0.6482 0.6035 0.6025
0.6458 0.6041 0.5995
0.5896 0.6039 0.5995
0.6522 0.6043 0.6041
0.2783 1 1
0.3286 0.6039 0.5995
0.3359 0.7776 1
0.1452 0.746 1
0.168 1 1
0.3359 1 1
0.1559 0.6039 0.6035
0.5879 0.6039 0.5995
0.168 1 1
0.1224 0.5134 0.5861
0.1331 0.6033 0.6033
0.5947 0.604 0.6029
0.6482 0.6035 0.6025
0.168 0.3013 0.3009
0.1445 0.6036 0.6036
0.1559 0.2818 0.6028
0.0735 0.587 0.587
0.1094 0.5132 0.5858
0.168 1 1
0.3359 0.3959 0.6027
0.168 0.3013 0.3009
0.6581 0.6036 0.6016
0.3359 0.7776 1
0.6522 0.6043 0.6041
0.6583 0.6039 0.5995
0.1453 0.4086 0.6027
0.1674 0.6036 0.6032
0.1461 0.604 0.604
0.6482 0.6035 0.6025
0.3359 0.6037 0.6023
0.0855 1 1
0.1445 0.3019 0.6029
0.2783 1 1
0.1608 0.4865 1
0.6519 0.5281 0.6031
0.6519 0.5281 0.6031
0.305 1 1
0.1429 0.6036 0.6036
0.1608 0.4865 1
0.2783 1 1
0.1355 0.4208 0.5312
0.6482 0.6035 0.6025
0.3359 1 1

Assayability

Assay information

  • Inhibition of Mycobacterium tuberculosis MshB by fluorescence-detected HPLC assay ChEMBL
  • Inhibition of Mycobacterium tuberculosis MshB by fluorescence-detected HPLC assay
  • ChEMBL
  • Activity at Mycobacterium tuberculosis MshB expressed in Escherichia coli BL21 at 250 uM assessed per mg of protein by HPLC analysis
  • ChEMBL
  • Activity at Mycobacterium tuberculosis MshB expressed in Escherichia coli BL21 by HPLC analysis
  • ChEMBL
  • Activity at Mycobacterium tuberculosis MshB expressed in Escherichia coli BL21 assessed per mg of protein by HPLC analysis
  • ChEMBL
  • Ratio of Kcat to Km for Mycobacterium tuberculosis MshB
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis MshB expressed in Escherichia coli BL21 at 500 uM after 10 mins by HPLC analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis MshB expressed in Escherichia coli BL21 after 10 mins by HPLC analysis

Reagent availability

No reagent availability information for this target.

Bibliographic References

2 literature references were collected for this gene.

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Gene identifier Rv1170 (Mycobacterium tuberculosis), N-acetyl-1-D-myo-inosityl-2-amino-2-deoxy-alpha-D-glucopyranoside deacetylase MshB (GlcNAc-Ins deacetylase)
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