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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: Aminoacyl-tRNA synthetases

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
PRS | proline--tRNA ligase | Plasmodium falciparum prolyl-tRNA synthetase | PfPRORS
Database Links Click here for help
ChEMBL Target
PlasmoDB
SynPHARM
UniProtKB
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 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 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)
compound 1 [PMID: 33929818] Small molecule or natural product Pf3D7 Parasite growth inhibition assay - - 8.0 pIC50 5
pIC50 8.0 (IC50 1x10-8 M) DAPI incorporation assay (72h) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product PfTM90C2B Parasite growth inhibition assay - - 7.8 pIC50 5
pIC50 7.8 (IC50 1.7x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product PfNF54 Parasite growth inhibition assay - - 7.7 pIC50 5
pIC50 7.7 (IC50 1.8x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Pf7G8 Parasite growth inhibition assay - - 7.7 pIC50 5
pIC50 7.7 (IC50 1.8x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product PfK1 Parasite growth inhibition assay - - 7.7 pIC50 5
pIC50 7.7 (IC50 2x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [5]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product PfDd2 Parasite growth inhibition assay - - 7.6 pIC50 5
pIC50 7.6 (IC50 2.4x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [5]
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]

5. Okaniwa M, Shibata A, Ochida A, Akao Y, White KL, Shackleford DM, Duffy S, Lucantoni L, Dey S, Striepen J et al.. (2021) Repositioning and Characterization of 1-(Pyridin-4-yl)pyrrolidin-2-one Derivatives as Plasmodium Cytoplasmic Prolyl-tRNA Synthetase Inhibitors. ACS Infect Dis, 7 (6): 1680-1689. [PMID:33929818]

How to cite this page

Aminoacyl-tRNA synthetases: Plasmodium falciparum proline--tRNA ligase. Last modified on 31/08/2021. Accessed on 29/11/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3056.