Plasmodium falciparum lysine--tRNA ligase | Antimalarial targets | IUPHAR/MMV Guide to MALARIA PHARMACOLOGY

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Plasmodium falciparum lysine--tRNA ligase

Target id: 3059

Nomenclature: Plasmodium falciparum lysine--tRNA ligase

Abbreviated Name: PfKRS1

Family: Antimalarial targets

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Plasmodium falciparum 3D7 - 583 KRS1 lysine--tRNA ligase
Previous and Unofficial Names
Plasmodium falciparum lysyl-tRNA synthetase
Database Links
ChEMBL Target
UniProtKB
Selected 3D Structures
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] 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] 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] 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] 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] 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] 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 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 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 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 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 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
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. Two distinct lysl-tRNA synthetases are encoded by the malaria parasite genome and are involved in translation in either the cytoplasm (PfKRS1) or in the apicoplast (PfKRS2).

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. U.S.A., 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]

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 lysine--tRNA ligase. Last modified on 12/06/2019. Accessed on 18/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=3059.