{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Yang G"],"funding":["Guangdong Natural Science Foundation","Shenzhen Science and Technology Innovation Commission","National Natural Science Foundation of China","National Key Research and Development Program of China"],"pagination":["4751"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11084299"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(9)"],"pubmed_abstract":["Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified <i>Plasmodium falciparum</i> tyrosyl-tRNA synthetase (<i>Pf</i>TyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against <i>Pf</i>TyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for <i>Pf</i>TyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within <i>Pf</i>TyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of <i>Plasmodium falciparum</i> in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by <i>P. falciparum</i>."],"journal":["International journal of molecular sciences"],"pubmed_title":["Competitive Inhibition of Okanin against <i>Plasmodium falciparum</i> Tyrosyl-tRNA Synthetase."],"pmcid":["PMC11084299"],"funding_grant_id":["2021YFC2300100","2021B1515020047","32271314","JCYJ20200109142446804","ZDSYS20230626091203007"],"pubmed_authors":["Weng Q","Sun L","Yang G","Li X","Li Z","Qian Y","Liang Y","Qin Y","Yan Y","Cheng Y"],"additional_accession":[]},"is_claimable":false,"name":"Competitive Inhibition of Okanin against <i>Plasmodium falciparum</i> Tyrosyl-tRNA Synthetase.","description":"Malaria is a severe disease that presents a significant threat to human health. As resistance to current drugs continues to increase, there is an urgent need for new antimalarial medications. Aminoacyl-tRNA synthetases (aaRSs) represent promising targets for drug development. In this study, we identified <i>Plasmodium falciparum</i> tyrosyl-tRNA synthetase (<i>Pf</i>TyrRS) as a potential target for antimalarial drug development through a comparative analysis of the amino acid sequences and three-dimensional structures of human and plasmodium TyrRS, with particular emphasis on differences in key amino acids at the aminoacylation site. A total of 2141 bioactive compounds were screened using a high-throughput thermal shift assay (TSA). Okanin, known as an inhibitor of LPS-induced TLR4 expression, exhibited potent inhibitory activity against <i>Pf</i>TyrRS, while showing limited inhibition of human TyrRS. Furthermore, bio-layer interferometry (BLI) confirmed the high affinity of okanin for <i>Pf</i>TyrRS. Molecular dynamics (MD) simulations highlighted the stable conformation of okanin within <i>Pf</i>TyrRS and its sustained binding to the enzyme. A molecular docking analysis revealed that okanin binds to both the tyrosine and partial ATP binding sites of the enzyme, preventing substrate binding. In addition, the compound inhibited the production of <i>Plasmodium falciparum</i> in the blood stage and had little cytotoxicity. Thus, okanin is a promising lead compound for the treatment of malaria caused by <i>P. falciparum</i>.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Apr","modification":"2026-05-20T03:19:39.323Z","creation":"2026-05-20T03:08:14.959Z"},"accession":"S-EPMC11084299","cross_references":{"pubmed":["38731970"],"doi":["10.3390/ijms25094751"]}}