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Plasmodium falciparum proline--tRNA ligase

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Target id: 3056

Nomenclature: Plasmodium falciparum proline--tRNA ligase

Abbreviated Name: PfPRS

Family: Antimalarial targets

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 746 PRS proline--tRNA ligase
Previous and Unofficial Names Click here for help
Plasmodium falciparum prolyl-tRNA synthetase | PfPRORS
Database Links Click here for help
ChEMBL Target CHEMBL3301560 (Pf3D7)
PlasmoDB PF3D7_1213800 (Pf3D7)
SynPHARM 85927 (in complex with halofuginone)
UniProtKB Q8I5R7 (Pf3D7)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Prolyl-tRNA Synthetase (PRS) from Plasmodium falciparum in complex with Halofuginone and AMPPNP
PDB Id:  4YDQ
Ligand:  halofuginone
Resolution:  2.3Å
Species:  Plasmodium falciparum
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Prolyl-tRNA Synthetase (PRS) from Plasmodium falciparum
PDB Id:  4TWA
Resolution:  3.0Å
Species:  Plasmodium falciparum
References:  2
Whole Organism Assay Data Linked to This Target
Key to terms and symbols Click column headers to sort
Ligand Sp. Assay description Type Action Value Parameter Reference
halofuginone Small molecule or natural product Ligand has a PDB structure PfDd2

Plasmodium falciparum Dd2

P. falciparum strain Dd2 (PfDd2) is a clone derived from PfW2, following continuous culture in mefloquine. PfW2 was cloned from the Indochina III/CDC isolate, originally derived from a Laotian patient who failed chloroquine therapy.
PfDd2 can be obtained from the Malaria Research and Reference Reagent Resource Center (MR4) and is reported to be resistant to chloroquine, pyrimethamine and mefloquine.
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 Parasite growth inhibition assay - - 9.1 pEC50 1
⤷ pEC50 9.1 (EC50 8.1x10-10 M) SYBR Green assay [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
halofuginone Small molecule or natural product Ligand has a PDB structure Pf3D7

Plasmodium falciparum 3D7

P. falciparum strain 3D7 (Pf3D7) was derived from isolate NF54 by limiting dilution. The complete genome of Pf3D7 has been sequenced (GenBank: LN999946.1).
Pf3D7 can be obtained from the European Malaria Reagent Repository or the Malaria Research and Reference Reagent Resource Center (MR4) and is sensitive to a panel of antimalarial compounds including chloroquine and pyrimethamine.
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 Parasite growth inhibition assay - - 9.1 pEC50 1
⤷ pEC50 9.1 (EC50 8.6x10-10 M) SYBR Green assay [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
The aminoacyl-tRNA synthetases are emerging targets for antimalarial agents [4]. Although sharing a common tRNA esterification catalytic activity, these proteins are structurally diverse and physiologically distinct enzymes.

References

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1. Herman JD, Pepper LR, Cortese JF, Estiu G, Galinsky K, Zuzarte-Luis V, Derbyshire ER, Ribacke U, Lukens AK, Santos SA et al.. (2015) The cytoplasmic prolyl-tRNA synthetase of the malaria parasite is a dual-stage target of febrifugine and its analogs. Sci Transl Med, 7 (288): 288ra77. [PMID:25995223]

2. Jain V, Kikuchi H, Oshima Y, Sharma A, Yogavel M. (2014) Structural and functional analysis of the anti-malarial drug target prolyl-tRNA synthetase. J. Struct. Funct. Genomics, 15 (4): 181-90. [PMID:25047712]

3. Jain V, Yogavel M, Oshima Y, Kikuchi H, Touquet B, Hakimi MA, Sharma A. (2015) Structure of Prolyl-tRNA Synthetase-Halofuginone Complex Provides Basis for Development of Drugs against Malaria and Toxoplasmosis. Structure, 23 (5): 819-829. [PMID:25817387]

4. Manickam Y, Chaturvedi R, Babbar P, Malhotra N, Jain V, Sharma A. (2018) Drug targeting of one or more aminoacyl-tRNA synthetase in the malaria parasite Plasmodium falciparum. Drug Discov. Today, 23 (6): 1233-1240. [PMID:29408369]

How to cite this page

Antimalarial targets: Plasmodium falciparum proline--tRNA ligase. Last modified on 12/06/2019. Accessed on 19/01/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3056.