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Plasmodium falciparum prolyl-tRNA synthetase

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Target id: 3056

Nomenclature: Plasmodium falciparum prolyl-tRNA synthetase

Abbreviated Name: PfcPRS

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
Gene and Protein Information Comments
The Plasmodium genome encodes two forms of prolyl-tRNA synthetase, one found in the cytoplasm (PfcPRS, described here) and one in the apicoplast (PfaPRS, encoded by PF3D7_0925300).
Previous and Unofficial Names Click here for help
Pf3D7_12_v3:589,729..593,777(-) | PfProRS | PFL0670c | Plasmodium falciparum proline--tRNA ligase
Database Links Click here for help
Alphafold
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:  5
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:  4
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 Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 9.1 pEC50 3
pEC50 9.1 (EC50 8.1x10-10 M) SYBR Green assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
halofuginone Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 9.1 pEC50 3
pEC50 9.1 (EC50 8.6x10-10 M) SYBR Green assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf3D7 Parasite growth inhibition assay - - 8.0 pIC50 6
pIC50 8.0 (IC50 1x10-8 M) DAPI incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
halofuginone Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pb Parasite liver stage assay - - 7.8 pIC50 1
pIC50 7.8 (IC50 1.7x10-8 M) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfTM90C2B Parasite growth inhibition assay - - 7.8 pIC50 6
pIC50 7.8 (IC50 1.7x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfNF54 Parasite growth inhibition assay - - 7.7 pIC50 6
pIC50 7.7 (IC50 1.8x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf7G8 Parasite growth inhibition assay - - 7.7 pIC50 6
pIC50 7.7 (IC50 1.8x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfK1 Parasite growth inhibition assay - - 7.7 pIC50 6
pIC50 7.7 (IC50 2x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 1 [PMID: 33929818] Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 7.6 pIC50 6
pIC50 7.6 (IC50 2.4x10-8 M) [3H]-hypoxanthine incorporation assay (72h) [6]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
PfcPRS is ranked as a "High Priority" target in the Malaria Drug Accelerator (MalDA) portfolio [2].

References

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1. Derbyshire ER, Mazitschek R, Clardy J. (2012) Characterization of Plasmodium liver stage inhibition by halofuginone. ChemMedChem, 7 (5): 844-9. [PMID:22438279]

2. Forte B, Ottilie S, Plater A, Campo B, Dechering KJ, Gamo FJ, Goldberg DE, Istvan ES, Lee M, Lukens AK et al.. (2021) Prioritization of Molecular Targets for Antimalarial Drug Discovery. ACS Infect Dis, 7 (10): 2764-2776. [PMID:34523908]

3. 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]

4. 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]

5. 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]

6. 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 prolyl-tRNA synthetase. Last modified on 29/03/2022. Accessed on 06/12/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3056.