Detailed view for Rv2870c

Basic information

TDR Targets ID: 981510
Mycobacterium tuberculosis, Probable 1-deoxy-D-xylulose 5-phosphate reductoisomerase Dxr (DXP reductoisomerase) (1-deoxyxylulose-5-phosphate reductoisomeras
Source Database / ID:  Tuberculist 

pI: 5.5427 | Length (AA): 413 | MW (Da): 42821 | 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

No Pfam domain information for this protein.

Gene Ontology

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

Metabolic Pathways

Terpenoid backbone biosynthesis (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
11 388 4a03 (A) 11 388 99.99 0 1 2.14995 -1.45

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_130462)

Species Accession Gene Product
Arabidopsis thaliana AT5G62790   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Babesia bovis BBOV_III010740   1-deoxy-D-xylulose 5-phosphate reductoisomerase family protein
Chlamydia trachomatis CT_071   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Escherichia coli b0173   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Mycobacterium leprae ML1583c   PROBABLE 1-DEOXY-D-XYLULOSE 5-PHOSPHATE REDUCTOISOMERASE DXR (DXP REDUCTOISOMERASE) (1-DEOXYXYLULOSE-5-PHOSPHATE REDUCTOISOMERAS
Mycobacterium tuberculosis Rv2870c   Probable 1-deoxy-D-xylulose 5-phosphate reductoisomerase Dxr (DXP reductoisomerase) (1-deoxyxylulose-5-phosphate reductoisomeras
Mycobacterium ulcerans MUL_2085   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Neospora caninum NCLIV_051900   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Oryza sativa 4326153   Os01g0106900
Plasmodium berghei PBANKA_1330600   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Plasmodium falciparum PF3D7_1467300   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Plasmodium knowlesi PKNH_1214000   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Plasmodium vivax PVX_117100   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Plasmodium yoelii PY05578   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Toxoplasma gondii TGME49_214850   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Treponema pallidum TP0601   1-deoxy-D-xylulose 5-phosphate reductoisomerase
Theileria parva TP02_0073   1-deoxy-D-xylulose 5-phosphate reductoisomerase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0179   1-deoxy-D-xylulose 5-phosphate reductoisomerase

Essentiality

Rv2870c has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b0173 Escherichia coli essential goodall
PBANKA_1330600 Plasmodium berghei Essential plasmo
TGME49_214850 Toxoplasma gondii Probably essential sidik
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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • shigen Profiling of E. coli Chromosome (PEC) National Institute of Genetics, Japan
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

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

53 chemical compounds are associated with this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Mycobacterium smegmatis (strain ATCC 700084 / mc(2)155) 1-deoxy-D-xylulose 5-phosphate reductoisomerase Compounds References
Plasmodium falciparum 1-deoxy-D-xylulose 5-phosphate reductoisomerase Compounds References
Arabidopsis thaliana 1-deoxy-D-xylulose 5-phosphate reductoisomerase Compounds References
Escherichia coli 1-deoxy-D-xylulose 5-phosphate reductoisomerase Compounds References
Synechocystis sp. (strain PCC 6803 / Kazusa) 1-deoxyxylulose-5-phosphate reductoisomerase 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
0.0366 0.3554 1
0.0602 0.5899 0.5
0.089 0.9067 1
0.075 0.4803 1
0.1739 1 1
0.0873 1 0.5
0.1722 0.551 1
0.05 0.3578 1
0.1031 0.6088 0.5
0.0625 0.6068 1
0.05 1 1
0.5156 0.308 0.9691
0.6557 0.3828 0.7665
0.0626 0.4576 1
0.089 0.9069 1
1.0477 0.5182 0.7376
0.4294 0.3827 0.7664
0.1724 0.7435 1
0.1974 0.7479 0.5
0.3469 0.7669 0.5
0.3469 0.7669 0.5
0.1901 0.2726 0.5
0.0602 0.5899 0.5
0.1462 0.8085 1
0.0549 0.5153 0.5
0.346 0.7634 1
1.0224 0.4712 0.7387
0.1125 0.3616 0.5
0.2029 0.8839 0.5
0.346 0.7634 1
0.3281 0.8474 0.5
0.05 1 0.5
0.3099 0.413 1
0.346 0.7634 1
0.3561 0.5422 1
1.2269 0.5181 0.7388
0.3329 0.8285 1
0.0691797 0.729621 0.5
0.1372 0.3085 0.3303
0.8175 0.4314 0.7376
0.9791 0.4464 1
1.3523 0.5261 0.8978
0.1869 0.7134 0.5
0.3561 0.5422 1
0.7391 0.3905 1
0.346 0.7634 1
0.3483 0.9073 1
1.3523 0.5261 0.8978
0.2999 0.7374 0.5
0.2341 0.873 1
0.0595 0.6089 1
0.054 0.4803 1
0.0595 0.6089 1
0.5456 0.2564 0.4875
0.0527 0.4919 0.5
0.2362 0.781 1
0.1242 0.3307 1
0.224 1 0.5
0.05 0.3803 1
0.0653 0.4848 1
0.346 0.7634 1
0.2782 0.3383 0.3377
0.0595 0.6089 1
0.0885 0.5698 0.5
0.5803 0.3827 0.7664
0.0616 0.4615 0.5
0.1176 0.4552 0.5
0.1011 0.7261 1
1.3523 0.5261 0.8978
0.2396 0.2505 0.9742
0.0618 0.5891 1
0.0983 0.7244 1
0.2816 0.3617 1
0.1292 0.5 0.5
0.0249 0.972 0.5
0.1986 0.277 1
0.089 0.9067 1
0.0692 0.7118 1
0.2607 0.6263 1
0.107 0.4607 0.4503
0.0906 1 0.5
0.1998 0.7995 1
0.0625 0.598594 1
0.1242 0.3307 1
1.3523 0.5261 0.8978
0.2304 0.8658 1
0.4344 0.4303 0.7376
0.0595 0.6089 1
0.1198 0.5281 1
0.346 0.7634 1
0.0381 0.5739 0.691
0.278 0.6428 0.5
0.3561 0.6601 0.5
0.5156 0.308 0.9691
0.05 1 0.5
0.1739 1 1
0.3593 0.7214 1
0.2396 0.2505 0.9742
0.0549 0.5905 0.5
0.3561 0.5422 1
0.3185 0.789 0.5
0.0626 0.4576 1
0.9791 0.4464 1
0.8175 0.4314 0.7376
0.346 0.7634 1
0.346 0.7634 1
0.0605 0.3844 0.5
1.2269 0.5181 0.7388
0.5955 0.4083 1
1.2269 0.5181 0.7388
0.05 1 0.5
0.1317 0.485 1
0.0625 0.608454 0.5
0.3561 0.6601 0.5
0.346 0.7634 1
0.0513 0.5333 0.5
0.054 0.4803 1
0.1676 0.3764 1
0.05 1 0.5
0.05 0.3076 1
0.346 0.7634 1
0.3659 0.4616 1
0.2276 1 1
0.2607 0.3295 0.5
0.5415 0.5148 1
0.3152 0.599 0.5
0.3561 0.5422 1
0.05 1 1
0.3714 0.9071 1
0.3659 0.4616 1
0.5803 0.3828 0.7665
0.089 0.9067 1
0.3561 0.5422 1
0.0595 0.6089 1
0.2524 0.7047 1
0.4215 0.4303 0.7376
0.107 0.4607 0.4503
0.126769 0.299725 1
0.2396 0.2505 0.9742
0.2607 0.3295 0.5
0.0625 0.6068 1
0.1901 0.2726 0.5
0.4102 0.599 0.5
0.2524 0.7047 1
0.05 1 0.5
0.1125 0.3616 0.5
0.0625 0.587495 0.5
0.2988 1 1
0.0605 0.3844 0.5
0.0952 0.7316 0.5
0.8175 0.4314 0.7376
0.3561 0.5422 1
0.1998 0.7997 1
0.2199 1 0.5
0.0595 0.6089 1

Assayability

Assay information

  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR assessed as NADPH-dependent conversion of 1-deoxy-D-xylulose 5-phosphate to 2-C-methyl-D-erythritol 4-phosphate by spectrophotometric method
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant DXR expressed in Escherichia coli BL21 (DE3) using DXP as substrate and MgCl2 as cofactor preincubated for 10 mins
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant DXR expressed in Escherichia coli BL21 (DE3) using DXP as substrate and Mn2+ as cofactor preincubated for 10 mins
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis recombinant DXR expressed in Escherichia coli BL21 (DE3) using DXP as substrate and MgCl2 as cofactor at 100 uM preincubated for 10 mins
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR assessed as reduction of 1-deoxy-D-xylulose 5-phosphate into 2-C-methyl-D-erythritol-4-phosphate at 100 uM measured for every 5 secs upto 500 secs by spectrophotometry analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR assessed as reduction of 1-deoxy-D-xylulose 5-phosphate into 2-C-methyl-D-erythritol-4-phosphate measured for every 5 secs upto 500 secs by spectrophotometry analysis
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR using DXP as substrate assessed as formation of MEP measured every 5 secs for 180 secs by spectrophotometric analysis
  • ChEMBL
  • Binding affinity to Mycobacterium tuberculosis DXR assessed as dissociation constant by spectrofluorimetric analysis in presence of NADPH and MnCl2
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR using DXP as substrate at 100 uM measured every 5 secs for 250 secs in presence of NADPH relative to control
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis DXR using DXP as substrate measured every 5 secs for 250 secs in presence of NADPH
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis IspC by photometric assay
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis Dxr at 100 uM
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis Dxr
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis Dxr
  • ChEMBL
  • Inhibition of Mycobacterium tuberculosis IspC using 1-deoxy-D-xylulose 5-phosphate as substrate by photometric analysis
  • ChEMBL
  • Inhibition of recombinant Mycobacterium tuberculosis Dxr expressed in Escherichia coli BL21 CodonPlus (DE3)-RIL cells using DOXP as substrate assessed as NADPH oxidation at 100 uM by spectrophotometric analysis
  • ChEMBL
  • Inhibition of recombinant Mycobacterium tuberculosis Dxr expressed in Escherichia coli BL21 CodonPlus (DE3)-RIL cells using DOXP as substrate assessed as NADPH oxidation by spectrophotometric analysis

Reagent availability

No reagent availability information for this target.

Bibliographic References

No literature references available for this target.

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User comments

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Gene identifier Rv2870c (Mycobacterium tuberculosis), Probable 1-deoxy-D-xylulose 5-phosphate reductoisomerase Dxr (DXP reductoisomerase) (1-deoxyxylulose-5-phosphate reductoisomeras
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