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Plasmodium falciparum phenylalanyl-tRNA synthetase alpha subunit

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Target not currently curated in GtoImmuPdb

Malaria Pharmacology Ligand  Target has curated data in GtoMPdb

Target id: 2954

Nomenclature: Plasmodium falciparum phenylalanyl-tRNA synthetase alpha subunit

Abbreviated Name: PfcFRS

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 - 575 cPheRS phenylalanine--tRNA ligase alpha subunit
Gene and Protein Information Comments
The phenylalanyl-tRNA synthetases (FRSs) are unique within the aaRS family because the P. falciparum genome contains four genes that encode three distinct FRSs: cytosolic (heterodimeric cFRS; the α-subunit, described here; β-subunit, PF3D7_1104000), apicoplast (PF3D7_1232000), and mitochondrial FRS (PF3D7_0603700) [1,4].
Previous and Unofficial Names Click here for help
PfcPheRS | PFA0480w | Plasmodium falciparum phenylalanine--tRNA ligase alpha subunit
Database Links Click here for help
Alphafold
PlasmoDB
UniProtKB

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Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BRD7929 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf Inhibition 7.6 pIC50 3
pIC50 7.6 (IC50 2.3x10-8 M) [3]
BRD3444 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf Inhibition 7.3 pIC50 3
pIC50 7.3 (IC50 4.6x10-8 M) [3]
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
BRD3444 Small molecule or natural product Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 8.1 pEC50 3
pEC50 8.1 (EC50 9x10-9 M) SYBR Green I assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
BRD7929 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand PfDd2 Parasite growth inhibition assay - - 8.1 pEC50 3
pEC50 8.1 (EC50 9x10-9 M) SYBR Green I assay [3]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
BRD3444 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pb Parasite liver stage assay - - 6.8 pEC50 3
pEC50 6.8 (EC50 1.4x10-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [3]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
BRD7929 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pf3D7 Parasite late stage (IV–V) gametocyte assay - - 6.8 pEC50 3
pEC50 6.8 (EC50 1.6x10-7 M) [3]
BRD7929 Small molecule or natural product Ligand has a PDB structure Guide to Malaria Pharmacology Ligand Pb Parasite liver stage assay - - 6.8 pEC50 3
pEC50 6.8 (EC50 1.62x10-7 M) Luciferase bioluminescence assay to measure parasite invasion into HepG2 liver cells [3]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
BRD3444 Small molecule or natural product Guide to Malaria Pharmacology Ligand Pf3D7 Parasite late stage (IV–V) gametocyte assay - - 6.2 pEC50 3
pEC50 6.2 (EC50 6.63x10-7 M) [3]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
Malaria Pharmacology Comments
The three PfFRSs are class II aaRSs [1].
The aaRSs are emerging targets for antimalarial agents (reviewed in [4]), with PfcFRS the first member of the family whose inhibition results in elimination of asexual blood, liver and transmission-stage parasites [3]. PfcFRS is ranked as a "High Priority" target in the Malaria Drug Accelerator (MalDA) portfolio [2].

References

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1. Bhatt TK, Kapil C, Khan S, Jairajpuri MA, Sharma V, Santoni D, Silvestrini F, Pizzi E, Sharma A. (2009) A genomic glimpse of aminoacyl-tRNA synthetases in malaria parasite Plasmodium falciparum. BMC Genomics, 10: 644. [PMID:20042123]

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. Kato N, Comer E, Sakata-Kato T, Sharma A, Sharma M, Maetani M, Bastien J, Brancucci NM, Bittker JA, Corey V et al.. (2016) Diversity-oriented synthesis yields novel multistage antimalarial inhibitors. Nature, 538 (7625): 344-349. [PMID:27602946]

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

Aminoacyl-tRNA synthetases: Plasmodium falciparum phenylalanyl-tRNA synthetase alpha subunit. Last modified on 29/03/2022. Accessed on 29/09/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2954.