Detailed view for PF3D7_0810800

Basic information

TDR Targets ID: 1028
Plasmodium falciparum, hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase
Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 7.1076 | Length (AA): 706 | MW (Da): 83374 | Paralog Number: 0

Signal peptide: N | GPI Anchor: N | Predicted trans-membrane segments: 0

Druggability Group : DG4

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

PF00809   Pterin binding enzyme
PF01288   7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase (HPPK)

Gene Ontology

Mouse over links to read term descriptions.
GO:0042558   pteridine and derivative metabolic process  
GO:0006761   dihydrofolate biosynthetic process  
GO:0004156   dihydropteroate synthase activity  
GO:0003848   2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity  
GO:0044237   cellular metabolic process  
GO:0009396   folic acid and derivative biosynthetic process  

Metabolic Pathways

Folate biosynthesis (KEGG)
Global map (KEGG)

Structural information

Modbase 3D models:

There are 10 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
185 705 2bmb (A) 353 861 25.00 0 1 0.68 0.1
385 617 1tx2 (A) 16 228 40.00 0 1 0.79 -0.98
74 255 4uos (A) 2 177 23.00 0.00067 0.67 0.55819 -0.93
310 690 4pzv (A) 81 421 23.00 0 1 0.34296 1.36
380 702 1aj0 (A) 6 271 32.00 0 1 0.609907 -0.02
388 616 1ad1 (A) 3 210 38.00 0 1 0.648263 -0.09
74 255 4uos (A) 2 177 23.00 0.00081 0.81 0.58709 -1.07
123 706 3bof (A) 1 560 12.00 0 1 0.515195 0.89
380 702 1aj0 (A) 6 271 32.00 0 1 0.619807 -0.11
388 616 1ad1 (A) 3 210 38.00 0 1 0.651963 -0.13

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
Upper 80-100% percentile intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs. Otto TD
Upregulation Percent Ranking Stage Dataset
Upper 60-80% percentile intra-erythrocytic - 32 hs, early trophozoite, late ring, late trophozoite. Otto TD PlasmoDB
Upregulation Percent Ranking Stage Dataset
Mid 40-60% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 48 hs, sporozoite, early ring, early schizont, Oocyst, Ring. Otto TD PlasmoDB Zanghi G
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile intra-erythrocytic - 40 hs, Male Gametocyte. Otto TD Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 0-20% percentile Sporozoite, Female Gametocyte. Zanghi G 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.
  • Lasonder E Integrated transcriptomic and proteomic analyses of P. falciparum gametocytes. Molecular insight into sex-specific processes and translational repression.
  • Otto TD New insights into the blood-stage transcriptome of Plasmodium falciparum using RNA-Seq.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB

Orthologs

Ortholog group members (OG5_128803)

Species Accession Gene Product
Arabidopsis thaliana AT4G30000   Dihydropterin pyrophosphokinase / Dihydropteroate synthase
Arabidopsis thaliana AT1G69190   bifunctional hydroxymethyldihydropterinpyrophosphokinase/ dihydropteroate synthase
Candida albicans CaO19.8210   likely pterin binding enzyme similar to S. cerevisiae FOL1 (YNL256W) involved in folic acid and derivative biosynthesis
Candida albicans CaO19.579   likely pterin binding enzyme similar to S. cerevisiae FOL1 (YNL256W) involved in folic acid and derivative biosynthesis
Chlamydia trachomatis CT_613   bifunctional 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase/dihydropteroate synthase
Dictyostelium discoideum DDB_G0278283   dihydro-6-hydroxymethylpterin pyrophosphokinase
Escherichia coli b3177   7,8-dihydropteroate synthase
Mycobacterium leprae ML0224   Probable dihydropteroate synthase 1 FolP1 (DHPS 1) (dihydropteroate pyrophosphorylase 1) (dihydropteroate dipyrophosphorylase 1)
Mycobacterium tuberculosis Rv3608c   Dihydropteroate synthase 1 FolP (DHPS 1) (dihydropteroate pyrophosphorylase 1) (dihydropteroate diphosphorylase 1)
Mycobacterium ulcerans MUL_4190   dihydropteroate synthase 1 FolP1
Neospora caninum NCLIV_027230   Dihydropteroate synthase, related
Oryza sativa 4343919   Os07g0618500
Plasmodium berghei PBANKA_1426700   hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase, putative
Plasmodium falciparum PF3D7_0810800   hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase
Plasmodium knowlesi PKNH_1429900   hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase, putative
Plasmodium vivax PVX_123230   hydroxymethylpterin pyrophosphokinase-dihydropteroate synthetase, putative
Plasmodium yoelii PY02225   hypothetical protein
Plasmodium yoelii PY02226   dihydropteroate synthase, putative
Saccharomyces cerevisiae YNL256W   trifunctional dihydropteroate synthetase/dihydrohydroxymethylpterin pyrophosphokinase/dihydroneopterin aldolase FOL1
Toxoplasma gondii TGME49_259550   dihydropteroate synthase

Essentiality

PF3D7_0810800 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b3177 Escherichia coli essential goodall
YNL256W Saccharomyces cerevisiae inviable yeastgenome
PBANKA_1426700 Plasmodium berghei Essential plasmo
TGME49_259550 Toxoplasma gondii Probably essential sidik
Show/Hide essentiality data references
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database
  • 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.
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • 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.
  • keio Systematic single-gene knock-out mutants of E. coli K12 The Keio Collection
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • 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
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) decreased time (PATO:0000716) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) inferred from anti-sense experiment (ECO:0000018) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 8552672
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum 513479   561569  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15155224 9076734 9391132
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium vivax 513479   561569  
Annotator: saralph@unimelb.edu.au. Comment: 012/Mar/09. References: 15155224 9076734 9391132

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): 0.8

Known modulators for this target

Compound Source Reference
Curated by TDRTargets References
Curated by TDRTargets References

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Plasmodium berghei hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase, putative Compounds References
Escherichia coli 7,8-dihydropteroate synthase Compounds References
Bacillus anthracis Dihydropteroate synthase Compounds References
By sequence similarity to non orthologous druggable targets
Species Target Length Identity Alignment span Linked Drugs Reference
Bacteria Bacterial dihydropteroate synthase 282 aa 27.5% 316 aa Compounds References
Obtained from network model

Ranking Plot

Putative Drugs List

Compound Raw Global Species
0.0377 0.311 1
0.1939 0.3472 1
0.4473 0.3393 1
0.1273 0.3667 1
0.5348 0.3404 1
0.0313 0.3477 1
0.0652 1 1
0.031 0.8631 1
0.0754 1 1
0.0327 0.6154 1
0.0343 0.415 1
0.1402 0.2748 1
0.1823 0.2685 0.5
0.4359 1 1
0.0316 0.316 1
0.0348 0.6446 1
0.0377 1 1
0.5348 0.3404 1
0.3773 0.3094 1
0.4543 0.3104 1
0.0954 1 1
0.0343 0.4146 1
0.0303 1 1
0.0955 0.6907 0.5
0.0377 1 0.5
0.0333 1 1
0.0377 0.4791 1
0.3773 0.3094 1
0.4895 0.2536 0.5
0.0319 0.54 1
0.0981 1 1
0.4873 0.3212 0.5
0.0804 0.3475 1
0.4359 1 1
0.4092 0.2536 0.5
0.1796 0.2866 0.5
0.1188 0.264 0.5
0.5498 1 1
0.0385 0.2792 1
0.0954 1 1
0.0303 1 1
0.0302209 0.5 0.5
0.0347 0.4128 1
0.031 0.3508 1
0.1188 0.264 0.5
0.0377 0.5 0.5
0.0303 0.9895 0.5
0.5505 0.3332 0.5
0.0487 0.6736 1
0.0316 0.316 1
0.118 0.2844 1
0.4868 1 1
0.0311 0.6732 1
0.0311 0.6678 1
0.0427 1 0.5
0.3588 1 1
0.0541 0.4655 1
0.4543 0.3104 1
0.0319 0.3473 1
0.5027 0.3234 1
0.0323 1 1
0.0379 1 1
0.0541 0.3353 1
0.1962 0.3299 1
0.4359 1 1
0.0377 0.2505 0
0.0319 0.3473 1
0.0344 0.344 1
0.0304 1 1
0.3588 1 1
0.0327 0.3506 1
0.0377 0.5 0.5
0.0541 0.4188 0.5
0.0426761 0.303738 0.5
0.4491 1 1
0.0648 1 1
0.0311 0.6732 1
0.4359 1 1
0.0648 1 1
0.4359 1 1
0.0333 0.9414 1
0.0347 0.4128 1
0.4359 1 1
0.5505 0.3332 0.5
0.0377 1 1
0.5498 1 1
0.04 1 1
0.0366 0.6645 1
0.1365 0.2588 0.5
0.0668 1 0.5
0.0377 0.2701 1
0.3588 1 1
0.0343 0.4146 1
0.0941 0.4681 1
0.0343 0.4186 1
0.0346 0.4114 1
0.0366 0.6467 1
0.0377 0.5583 1
0.0311 0.6732 1
0.0377 0.2565 0.5
0.0673 0.2955 1
0.0667 1 0.5
0.0427 0.6228 0.5
0.0348 1 1
0.1382 1 0.5
0.0327 0.5395 1
0.0754 1 1
0.0377 1 0.5
0.3894 0.3329 1
0.0304 1 1
0.0377 1 0.5
0.4359 1 1
0.118 0.2844 1
0.0645 0.265 1
0.0673 0.5 0.5
0.0628 1 1
0.0319 0.3473 1
0.0427 1 1
0.0996 1 0.5
0.0723 0.2976 1
0.0307 0.9051 0.5
0.0333 0.8271 1
0.0668 1 0.5
0.0304 0.3714 1
0.0954 1 1
0.0303 0.5469 1
0.4023 0.2744 0.5
0.0336 0.6078 1
0.0728 0.5976 1
0.0377 0.4787 1
0.0312 1 1
0.0316 0.316 1

Assayability

Assay information

  • 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_0810800 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium chabaudi ( 4 )

Bibliographic References

136 literature references were collected for this gene.

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Gene identifier PF3D7_0810800 (Plasmodium falciparum), hydroxymethyldihydropterin pyrophosphokinase-dihydropteroate synthase
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