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Plasmodium falciparum lysine--tRNA ligase

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Target id: 3059

Nomenclature: Plasmodium falciparum lysine--tRNA ligase

Abbreviated Name: PfKRS1

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 - 583 KRS1 lysine--tRNA ligase
Previous and Unofficial Names Click here for help
Plasmodium falciparum lysyl-tRNA synthetase
Database Links Click here for help
ChEMBL Target
PlasmoDB
UniProtKB
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of P. falciparum Lysyl-tRNA synthetase
PDB Id:  4H02
Resolution:  2.905Å
Species:  Plasmodium falciparum
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of Lysyl-tRNA Synthetase from Plasmodium falciparum bound to a difluoro cyclohexyl chromone ligand
PDB Id:  6HCU
Ligand:  compound 5 [PMID: 30894487]
Resolution:  1.62Å
Species:  Plasmodium falciparum 3D7
References:  1
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
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure Pf3D7 Parasite growth inhibition assay - - 6.6 pEC50 1
pEC50 6.6 (EC50 2.7x10-7 M) SYBRgreen I [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure PfNF54 Parasite growth inhibition assay - - 6.4 pEC50 1
pEC50 6.4 (EC50 3.9x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure PfK1 Parasite growth inhibition assay - - 6.3 pEC50 1
pEC50 6.3 (EC50 5.1x10-7 M) [3H]-hypoxanthine incorporation [1]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure Pv Parasite liver stage assay - - 6.0 pEC50 1
pEC50 6.0 (EC50 9.5x10-7 M) [1]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure PfNF54 Parasite gamete formation assay - - <6.0 pEC50 1
pEC50 <6.0 (EC50 >1x10-6 M) [1]
Lifecycle stages: Plasmodium mosquito host stage (gametocyte, gamete, zygote, ookinete, oocyst, sporozoite)
compound 5 [PMID: 30894487] Small molecule or natural product Ligand has a PDB structure PfNF54 Parasite stage V gametocyte assay - - 5.0 pEC50 1
pEC50 5.0 (EC50 9.9x10-6 M) Saponin-lysis Sexual Stage Assay (SaLSSA) [1]
Lifecycle stages: Plasmodium sexual blood stage (gametocyte)
cladosporin Small molecule or natural product Ligand has a PDB structure Py Parasite liver stage assay - - 7.4 pIC50 2
pIC50 7.4 (IC50 3.91x10-8 M) Sporozoite hepatocyte invasion assay [2]
Lifecycle stages: Plasmodium liver stage (sporozoite, hepatic schizont, hepatic merozoite)
cladosporin Small molecule or natural product Ligand has a PDB structure Pf3D7 Parasite growth inhibition assay - - 7.3 pIC50 2
pIC50 7.3 (IC50 4.54x10-8 M) SYBR Green assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cladosporin Small molecule or natural product Ligand has a PDB structure PfD6 Parasite growth inhibition assay - - 7.1 pIC50 2
pIC50 7.1 (IC50 7.21x10-8 M) SYBR Green assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cladosporin Small molecule or natural product Ligand has a PDB structure PfK1 Parasite growth inhibition assay - - 7.1 pIC50 2
pIC50 7.1 (IC50 8.01x10-8 M) SYBR Green assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
cladosporin Small molecule or natural product Ligand has a PDB structure PfNF54 Parasite growth inhibition assay - - 7.1 pIC50 2
pIC50 7.1 (IC50 8.79x10-8 M) SYBR Green assay [2]
Lifecycle stages: Plasmodium asexual blood stage (erythrocytic merozoite, trophozoite, erythrocytic schizont)
Malaria Pharmacology Comments
Two distinct lysine--tRNA ligases are encoded by the malaria parasite genome and are involved in translation in either the cytoplasm (PfKRS1) or in the apicoplast (PfKRS2). PfKRS1 has been validated as a promising target for antimalarial drug development.

References

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1. Baragaña B, Forte B, Choi R, Nakazawa Hewitt S, Bueren-Calabuig JA, Pisco JP, Peet C, Dranow DM, Robinson DA, Jansen C et al.. (2019) Lysyl-tRNA synthetase as a drug target in malaria and cryptosporidiosis. Proc Natl Acad Sci USA, 116 (14): 7015-7020. [PMID:30894487]

2. Hoepfner D, McNamara CW, Lim CS, Studer C, Riedl R, Aust T, McCormack SL, Plouffe DM, Meister S, Schuierer S et al.. (2012) Selective and specific inhibition of the plasmodium falciparum lysyl-tRNA synthetase by the fungal secondary metabolite cladosporin. Cell Host Microbe, 11 (6): 654-63. [PMID:22704625]

3. Khan S, Garg A, Camacho N, Van Rooyen J, Kumar Pole A, Belrhali H, Ribas de Pouplana L, Sharma V, Sharma A. (2013) Structural analysis of malaria-parasite lysyl-tRNA synthetase provides a platform for drug development. Acta Crystallogr D Biol Crystallogr, 69 (Pt 5): 785-95. [PMID:23633587]

How to cite this page

Aminoacyl-tRNA synthetases: Plasmodium falciparum lysine--tRNA ligase. Last modified on 19/02/2021. Accessed on 14/05/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3059.