Detailed view for Rv3266c

Basic information

TDR Targets ID: 7016
Mycobacterium tuberculosis, dTDP-6-deoxy-L-lyxo-4-hexulose reductase RmlD (dTDP-rhamnose modification protein) (dTDP-rhamnose biosynthesis protein) (dTDP-rh
Source Database / ID:  Tuberculist 

pI: 6.8388 | Length (AA): 304 | MW (Da): 32045 | 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

PF04321   RmlD substrate binding domain

Gene Ontology

Mouse over links to read term descriptions.
GO:0003824   catalytic activity  
GO:0008831   dTDP-4-dehydrorhamnose reductase activity  
GO:0005488   binding  
GO:0045226   extracellular polysaccharide biosynthetic process  
GO:0008152   metabolic process  

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 38 1bdb (A) 1 38 32.00 0.46 0.18 0.4909 -0.52
4 61 3dhn (A) 3 74 24.00 0.0019 0.97 0.375689 -1.12
6 302 1kew (A) 1 347 20.00 0 1 1.05987 0.03
6 287 1vl0 (A) 1 276 37.00 0 1 1.40253 -0.59

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
Mid 40-60% percentile Dormant phase. hasan
Upregulation Percent Ranking Stage Dataset
Lower 0-20% 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_128895)

Species Accession Gene Product
Arabidopsis thaliana AT4G00560   NAD(P)-binding Rossmann-fold superfamily protein
Dictyostelium discoideum DDB_G0280135   methionine adenosyltransferase regulatory beta subunit
Escherichia coli b2040   dTDP-4-dehydrorhamnose reductase subunit, NAD(P)-binding, of dTDP-L-rhamnose synthase
Homo sapiens ENSG00000038274   methionine adenosyltransferase II, beta
Mycobacterium leprae ML0751   dTDP-6-deoxy-L-lyxo-4-hexulose reductase RmlD (dTDP-RHAMNOSE MODIFICATION PROTEIN) (dTDP-RHAMNOSE BIOSYNTHESIS PROTEIN) (dTDP-RH
Mus musculus ENSMUSG00000042032   methionine adenosyltransferase II, beta
Mycobacterium tuberculosis Rv3266c   dTDP-6-deoxy-L-lyxo-4-hexulose reductase RmlD (dTDP-rhamnose modification protein) (dTDP-rhamnose biosynthesis protein) (dTDP-rh
Mycobacterium ulcerans MUL_2612   dTDP-6-deoxy-L-lyxo-4-hexulose reductase RmlD
Oryza sativa 4331215   Os02g0826200
Schmidtea mediterranea mk4.059329.01  
Schmidtea mediterranea mk4.000705.07  
Trichomonas vaginalis TVAG_357160   NAD dependent epimerase/dehydratase, putative

Essentiality

Rv3266c has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b2040 Escherichia coli non-essential goodall
Show/Hide essentiality data references
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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
  • 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.

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): 0.5

Known modulators for this target

Compound Source Reference
ChEMBL23 References
ChEMBL23 References
ChEMBL23 References
References

Predicted associations

By orthology with druggable targets
Non orthologous druggable targets
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
0.0246 0.5704 0.8891
0.0218 0.3147 1
0.0300186 0.643299 0
0.0182 0.2971 0.6183
0.0431 0.297 0.7565
0.0244 0.2558 0.7864
0.0463 0.3177 1
0.0456 0.5994 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis RmlC/RmlD expressed in Escherichia coli by spectrophotometry
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis RmlD assessed as inhibition of dTDP-beta-6-deoxy-L-lyxo-4-hexulose to dTDP-beta-L-rhamnose conversion
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis RmlD assessed as inhibition of dTDP-beta-6-deoxy-L-lyxo-4-hexulose to dTDP-beta-L-rhamnose conversion at 10 ug/ml

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 Rv3266c (Mycobacterium tuberculosis), dTDP-6-deoxy-L-lyxo-4-hexulose reductase RmlD (dTDP-rhamnose modification protein) (dTDP-rhamnose biosynthesis protein) (dTDP-rh
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