Detailed view for PF3D7_0513300

Basic information

TDR Targets ID: 4164
Plasmodium falciparum, purine nucleoside phosphorylase

Source Database / ID:  PlasmoDB   |   GeneDB   |   MPMP

pI: 6.4712 | Length (AA): 245 | MW (Da): 26858 | 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

PF01048   Phosphorylase superfamily

Gene Ontology

Mouse over links to read term descriptions.
GO:0004850   uridine phosphorylase activity  
GO:0003824   catalytic activity  
GO:0009116   nucleoside metabolic process  

Metabolic Pathways

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
1 245 2bsx (A) 1 245 99.99 0 1 2.19 -1.64
2 244 2b94 (A) 0 241 82.00 0 1 2.04 -1.78
1 245 2bsx (A) 1 245 99.99 0 1 2.2047 -1.31
1 244 3emv (A) 1 245 82.00 0 1 2.03922 -1.31

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:

  • 1NW4:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 1Q1G:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 1SQ6:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 2B94:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 2BSX:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3EMV:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3ENZ:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3FOW:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 3PHC:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6AQS:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date
  • 6AQU:
  • Resolution Method # Atoms # Residues Dep. Date Pub. Date Mod. Date

Expression

Upregulation Percent Ranking Stage Dataset
Upper 80-100% percentile intra-erythrocytic - 0 hs, intra-erythrocytic - 8 hs, intra-erythrocytic - 16 hs, intra-erythrocytic - 24 hs, intra-erythrocytic - 32 hs, intra-erythrocytic - 40 hs, intra-erythrocytic - 48 hs, gametocyte, merozoite, sporozoite, early ring, early schizont, early trophozoite, late ring, late schizont, late trophozoite, Oocyst, Ring, Female Gametocyte. Otto TD PlasmoDB Zanghi G Lasonder E
Upregulation Percent Ranking Stage Dataset
Lower 20-40% percentile Sporozoite, Male 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.
  • PlasmoDB Data on upregulation of P. falciparum genes in different life cycle stages, combined from several microarray experiments available in PlasmoDB
  • 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.

Orthologs

Ortholog group members (OG5_130516)

Species Accession Gene Product
Babesia bovis BBOV_III005140   phosphorylase family protein
Dictyostelium discoideum DDB_G0284431   uridine phosphorylase
Drosophila melanogaster Dmel_CG17224   CG17224 gene product from transcript CG17224-RC
Escherichia coli b4384   purine-nucleoside phosphorylase
Entamoeba histolytica EHI_130960   purine nucleoside phosphorylase, putative
Entamoeba histolytica EHI_130930   purine nucleoside phosphorylase, putative
Neospora caninum NCLIV_053130   hypothetical protein
Plasmodium berghei PBANKA_1113000   purine nucleoside phosphorylase, putative
Plasmodium falciparum PF3D7_0513300   purine nucleoside phosphorylase
Plasmodium knowlesi PKNH_1019800   purine nucleoside phosphorylase, putative
Plasmodium vivax PVX_080575   purine nucleoside phosphorylase, putative
Plasmodium yoelii PY04622   purine nucleoside phosphorylase
Toxoplasma gondii TGME49_307030   Purine nucleoside phosphorylase
Treponema pallidum TP1027   uridine phosphorylase (udp)
Treponema pallidum TP0734   purine nucleoside phosphorylase (deoD)
Theileria parva TP02_0437   purine nucleoside phosphorylase, putative
Theileria parva TP02_0440   purine nucleoside phosphorylase, putative
Theileria parva TP02_0438   purine nucleoside phosphorylase, putative
Trichomonas vaginalis TVAG_127180   purine nucleoside phosphorylase, putative
Trichomonas vaginalis TVAG_454490   purine nucleoside phosphorylase, putative

Essentiality

PF3D7_0513300 has one or more orthologs with essentiality data
Gene/Ortholog Organism Phenotype Source Study
b4384 Escherichia coli non-essential goodall
PBANKA_1113000 Plasmodium berghei Essential plasmo
TGME49_307030 Toxoplasma gondii Probably non-essential sidik
Show/Hide essentiality data references
  • 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.
  • wormbase C. elegans RNAi experiments WormBase web site, http://www.wormbase.org, release WS170
  • 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.
  • 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
  • alsford High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res 2011, 21:915-924
  • neb C. elegans RNAi phenotypes Data obtained from Wormbase WS150, curated by K. Chaudary and T. Carlow, New England Biolabs
  • nmpdr Genome-scale essentiality datasets from published studies (M. tuberculosis) National Microbial Pathogen Data Resource
  • 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.
  • blattner Systematic mutagenesis of the E. coli (MG1655) genome J Bacteriol 2004, 186:4921-4930
  • yeastgenome Systematic deletion of yeast genes Saccharomyces Genome Database

Phenotypes and Validation (curated)

Annotated phenotypes:

Affected Entity Phenotypic quality Occurs in Occurs at Evidence Observed in Drugs/Inhibitors
growth (GO:0040007) lethal (sensu genetics) (PATO:0000718) multi-cellular organism (CARO:0000012) bloodstream stage (PLO:0040) in vivo inhibition (TDR:00016) Plasmodium falciparum No drug identifiers listed for this gene.
Annotator: saralph@unimelb.edu.au. Comment: Drug: (5'-Methylthio-immucillin-H). . References: 15576366

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

57 chemical compounds are associated with this gene

Predicted associations

By orthology with druggable targets
Species Known druggable target Linked compounds Reference
Toxoplasma gondii Purine nucleoside phosphorylase 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
0.0167 0.3902 1
0.365 0.825 0.5
0.018 0.643 0.5
0.0451 0.9877 0.5
0.018 0.5 0.5
0.0146 0.3007 0.5
0.2564 0.2906 0.5
0.4298 0.383 1
0.1741 0.8258 0.5
0.018 0.3007 0.5
0.4643 0.8049 1
0.4428 0.4025 1
0.016 0.3007 0.5
0.0451 0.9877 0.5
0.0319 1 0.5
0.018 0.3007 0.5
0.0175 0.3304 0.5
0.047 0.8385 0.5
0.4311 0.7679 0.5
0.0211 1 0.5
0.2349 0.2613 0.5
0.0330744 0.481619 1
0.4133 0.8116 1
0.0147 0.32 1
0.196 0.8458 0.5
0.0568 0.2609 1
0.4058 0.3709 0.5
0.3627 0.7741 1
0.0211 1 0.5
0.3872 0.7864 1
0.1734 0.6451 1
0.3965 0.8137 1
0.0152 0.3736 1
0.0211 1 0.5
0.4343 0.3029 1
0.0216 0.285 0.5
0.1372 0.8147 0.5
0.3872 0.7864 1
0.1743 0.8336 1
0.4592 0.802 0.5
0.018 0.3007 0.5
0.0261 0.3959 0.5
0.018 0.7599 1
0.3959 0.8038 1
0.018 0.7599 1
0.0172 0.7692 1
0.0159 0.3007 0.5
0.2446 0.806 0.5
0.0211 1 0.5
0.0243 1 0.5
0.4298 0.383 1
0.0211 1 0.5
0.0211 1 0.5
0.0152 0.3736 1
0.4058 0.3709 0.5
0.4428 0.4025 1
0.0789 0.6984 1
0.0719 0.3598 0.5
0.0407 0.2888 1
0.4018 0.5238 1
0.0921 0.8899 1
0.0223 0.2518 0.1878
0.0295 0.2611 1
0.3696 0.7306 1
0.3872 0.7864 1
0.0153 0.6136 1
0.0197 0.5105 0.4077
0.0151 1 1
0.0211 1 0.5
0.0243 1 0.5
0.1365 0.3996 1
0.3199 0.7981 1
0.4116 0.8263 1
0.0211 1 0.5
0.0211 1 0.5
0.07 0.3377 0.5
0.0146 1 0.5
0.018 0.643 0.5
0.0197 0.5105 0.4077
0.4644 0.7912 1
0.0243 1 0.5
0.4044 0.7351 0.5
0.2536 0.8786 1
0.4133 0.8116 1
0.4031 0.7833 1
0.3113 0.8199 1
0.4412 0.7191 0.5
0.018 0.3007 0.5
0.0211 1 0.5
0.2982 0.8108 0.5
0.4298 0.383 1
0.0144 0.2545 1
0.4455 0.7578 0.5
0.0261 0.3959 0.5
0.0164 0.41 0.5
0.365 0.825 0.5
0.2536 0.8786 1
0.3983 0.7961 0.5
0.0211 1 0.5
0.4298 0.383 1
0.0211 1 0.5
0.4697 0.7926 1
0.3872 0.7864 1
0.1365 0.3996 1
0.0991 0.8829 0.5
0.1734 0.6451 1
0.0211 1 0.5
0.0568 0.2609 1
0.018 0.3007 0.5
0.4695 0.8006 1
0.1734 0.6451 1
0.018 0.3007 0.5
0.0492 0.3293 1

Assayability

Assay information

  • Assay for Nucleoside Phosphorylase (2.4.2.1 ) Sigma-Aldrich
  • Automatic link to known assays based on EC numbers.
  • Inhibition of Plasmodium falciparum PNP ChEMBL
  • Inhibition of Plasmodium falciparum PNP
  • ChEMBL
  • BindingDB_Patents: Inhibition Assay. The inhibitor dissociation constants reported in Table 1 below are for phosphorolysis of inosine by PNP and were based on reaction rates measurements with different inhibitor concentrations. Reactions were started by addition of 0.05 ug of human or Plasmodium falciparum purine nucleoside phosphaorylase (HsPNP and PfPNP, respectively; final concentration 1.4 nM) to 1 mM inosine in 50 mM KPO4, pH=7.5 buffer with xanthine oxidase added to final concentration 60 mU/mL at 25 C. In the coupled assay, hypoxanthine formed by phosphorolysis of inosine was oxidized to uric acid and followed spectrophotometrically at 293 nm (extinction coefficient for uric acid epsilon(293)=12.9 mM-1). The dissociation constant for slow-onset tight-binding inhibitors was determined from reaction rates after slow onset inhibition had occurred according to the equation u =(kcat x S)/(Km(1+l/Kd)+S), where u  is the steady state reaction rate after the slow-onset inhibition period has reached equilibrium.
  • ChEMBL
  • BindingDB_Patents: ADP-Glo Kinase Assay. Inhibitor Concentration at 50% enzyme inhibition (IC50) values were calculated by quantifying the end-point ADP production from each kinase reaction using the ADP-Glo Kinase Assay (Promega, Madison, Wis.) as described by the manufacturer. Reactions were performed in Tris buffer (50 mM pH 7.5, RT) containing 20 mM MgCl2 and 0.1% Bovine Serum Albumin. Each assay was performed in 60 uL of the solution in 10x75 mm borosilicate glass test tubes and allowed to continuously shake during the duration of the assay. The total ADP generated was quantified by transferring 25 uL (2x) of each assay to a 96-well luminescence assay plate, followed by the addition of 25 uL of ADP-Glo Reagent (45 min incubation) to remove any remaining ATP. For luminescence readings, 50 uL of Kinase Detection Reagent (45 min incubation) was added to convert the ADP generated from the kinase reaction to ATP, and luminescent intensity was measured using a luciferase/luciferin reaction.
  • ChEMBL
  • Inhibition of Plasmodium falciparum purine nucleoside phosphorylase assessed as slow onset inhibition constant by xanthine-oxidase coupled assay
  • ChEMBL
  • Inhibition of Plasmodium falciparum purine nucleoside phosphorylase by xanthine-oxidase coupled assay
  • ChEMBL
  • Inhibition of Plasmodium falciparum PNP expressed in Escherichia coli BL21(DE3) cells by spectrophotometry
  • ChEMBL
  • Inhibition of recombinant Plasmodium falciparum PNP using inosine as substrate by xanthine oxidase coupling enzyme assay
  • ChEMBL
  • Inhibition of recombinant Plasmodium falciparum PNP using inosine as substrate assessed as inhibition constant for slow onset inhibition of enzyme-inhibitor complex by xanthine oxidase coupling enzyme assay
  • BRENDA Assay
  • An enzyme with this EC number or name or sequence has been assayed in Plasmodium falciparum ( 2 )

Reagent availability

  • Pfal008421AAA;
  • Type Source Notes
    soluble recombinant protein Structural Genomics for Pathogenic Protozoa (SGPP) Pfal008421; Recombinant protein: full-length; Source: P falciparum; uridine phosphorylase, putative ;
  • Reagent:
  • Target Type Source Notes
    PF3D7_0513300 purified protein BRENDA A protein with this EC number or name or sequence has been purified from Plasmodium lophurae ( 1 )

Bibliographic References

18 literature references were collected for this gene.

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Gene identifier PF3D7_0513300 (Plasmodium falciparum), purine nucleoside phosphorylase
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