Detailed view for PF3D7_0209300

Basic information

TDR Targets ID: 3360
Plasmodium falciparum, 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 9.9675 | Length (AA): 240 | MW (Da): 27161 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 1

Druggability Group : DG3

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

PF02542   YgbB family

Gene Ontology

Mouse over links to read term descriptions.
GO:0020011   apicoplast  
GO:0008685   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase activity  
GO:0016114   terpenoid biosynthetic process  

Structural information

Modbase 3D models:

There are 6 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
52 235 1w55 (A) 174 363 34.00 0 1 1.16 -0.58
64 238 1t0a (A) 3 159 39.00 0 1 1.22 -1.25
71 235 1w55 (A) 197 363 38.00 0 1 1.26 -1.19
25 235 1w55 (A) 157 363 34.00 0 1 1.24667 0.34
60 239 4c81 (A) 60 239 99.00 0 1 1.757 -0.74
116 235 2uzh (A) 38 154 29.00 0.0000000096 1 0.9672 -1.08

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
  • 3B6N:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4C81:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
PDB tag
  • 4C82:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, early schizont, early trophozoite, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 48 hs, late schizont, Oocyst, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, Sporozoite. Otto TD Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Female Gametocyte, Male Gametocyte. Lasonder E
Show/Hide expression data references
  • Zanghi G A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.

Orthologs

Ortholog group members (OG5_130616)

Species Accession Gene Product
Arabidopsis thaliana AT1G63970   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Babesia bovis BBOV_IV002810   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, putative
Chlamydia trachomatis CT_434   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Escherichia coli b2746   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Mycobacterium leprae ML0322   Probable 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase IspF (MECPS) (MECDP-synthase )
Mycobacterium tuberculosis Rv3581c   Probable 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase IspF (MECPS)
Mycobacterium ulcerans MUL_4157   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Neospora caninum NCLIV_029230   hypothetical protein
Oryza sativa 4330320   Os02g0680600
Plasmodium berghei PBANKA_0306400   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, putative
Plasmodium falciparum PF3D7_0209300   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
Plasmodium knowlesi PKNH_0411800   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, putative
Plasmodium vivax PVX_003920   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, putative
Plasmodium yoelii PY00321   YgbB family, putative
Toxoplasma gondii TGME49_255690   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase domain-containing protein
Treponema pallidum TP0512   hypothetical protein
Theileria parva TP03_0365   2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase, putative
Wolbachia endosymbiont of Brugia malayi Wbm0409   2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase

Essentiality

PF3D7_0209300 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b2746 Escherichia coli essential goodall
TGME49_255690 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • 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
  • gerdes Experimental determination and system-level analysis of essential genes in E. coli MG1655 Gerdes et al., J Bacteriol. 2003 185:5673-84
  • 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.
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
catalytic activity (GO:0003824) decreased (PATO:0000468) in vitro (MI:0492) inferred from specific protein inhibition (ECO:0000020) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: cytidyl-erythritol analogues. . References: 16392111

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
Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase Compounds References
Arabidopsis thaliana 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase Compounds References
Mycobacterium tuberculosis Probable 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase IspF (MECPS) 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
0.1068 0.2803 1
0.1068 0.3162 1
0.1058 0.3556 1
0.0652 0.3015 1
0.1068 0.2548 1
0.066 0.3051 1
0.0592 0.4733 1
0.1075 0.2822 1
0.1071 0.2793 1
0.1046 0.2772 1
0.0658 1 1
0.1065 0.2884 1
0.1065 0.2884 1
0.1071 0.2793 1
0.0668 0.3071 1
0.1065 0.2883 1
0.1068 0.3549 1
0.0657 0.3029 1
0.1046 0.2772 1
0.0744 0.3186 1
0.0592 0.4733 1
0.0744 0.2509 1
0.107 0.2914 1
0.1058 0.4548 1
0.0742 0.2521 1

Assayability

Assay information

  • Assay for Adenylate Cyclase (4.6.1.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 2 )

Reagent availability

  • Reagent:
  • Target Type Source Notes
    PF3D7_0209300 cloned gene BRENDA A gene with this EC number or name or sequence has been cloned from Plasmodium falciparum ( 3 )

Bibliographic References

15 literature references were collected for this gene.

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Gene identifier PF3D7_0209300 (Plasmodium falciparum), 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase
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