Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis.
Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections ar...
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ftdoajarticles:oai:doaj.org/article:3c793b7282b5484696cf5feb6c8202ff 2023-05-15T15:08:56+02:00 Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. Arvind Sharma Manmohan Sharma Manickam Yogavel Amit Sharma 2016-11-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0005084 https://doaj.org/article/3c793b7282b5484696cf5feb6c8202ff EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC5091859?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005084 https://doaj.org/article/3c793b7282b5484696cf5feb6c8202ff PLoS Neglected Tropical Diseases, Vol 10, Iss 11, p e0005084 (2016) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2016 ftdoajarticles https://doi.org/10.1371/journal.pntd.0005084 2022-12-31T02:44:16Z Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni. Article in Journal/Newspaper Arctic Human health Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 10 11 e0005084 |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Arvind Sharma Manmohan Sharma Manickam Yogavel Amit Sharma Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Helminth parasites are an assemblage of two major phyla of nematodes (also known as roundworms) and platyhelminths (also called flatworms). These parasites are a major human health burden, and infections caused by helminths are considered under neglected tropical diseases (NTDs). These infections are typified by limited clinical treatment options and threat of drug resistance. Aminoacyl-tRNA synthetases (aaRSs) are vital enzymes that decode genetic information and enable protein translation. The specific inhibition of pathogen aaRSs bores well for development of next generation anti-parasitics. Here, we have identified and annotated aaRSs and accessory proteins from Loa loa (nematode) and Schistosoma mansoni (flatworm) to provide a glimpse of these protein translation enzymes within these parasites. Using purified parasitic lysyl-tRNA synthetases (KRSs), we developed series of assays that address KRS enzymatic activity, oligomeric states, crystal structure and inhibition profiles. We show that L. loa and S. mansoni KRSs are potently inhibited by the fungal metabolite cladosporin. Our co-crystal structure of Loa loa KRS-cladosporin complex reveals key interacting residues and provides a platform for structure-based drug development. This work hence provides a new direction for both novel target discovery and inhibitor development against eukaryotic pathogens that include L. loa and S. mansoni. |
format |
Article in Journal/Newspaper |
author |
Arvind Sharma Manmohan Sharma Manickam Yogavel Amit Sharma |
author_facet |
Arvind Sharma Manmohan Sharma Manickam Yogavel Amit Sharma |
author_sort |
Arvind Sharma |
title |
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
title_short |
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
title_full |
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
title_fullStr |
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
title_full_unstemmed |
Protein Translation Enzyme lysyl-tRNA Synthetase Presents a New Target for Drug Development against Causative Agents of Loiasis and Schistosomiasis. |
title_sort |
protein translation enzyme lysyl-trna synthetase presents a new target for drug development against causative agents of loiasis and schistosomiasis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2016 |
url |
https://doi.org/10.1371/journal.pntd.0005084 https://doaj.org/article/3c793b7282b5484696cf5feb6c8202ff |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic Human health |
genre_facet |
Arctic Human health |
op_source |
PLoS Neglected Tropical Diseases, Vol 10, Iss 11, p e0005084 (2016) |
op_relation |
http://europepmc.org/articles/PMC5091859?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0005084 https://doaj.org/article/3c793b7282b5484696cf5feb6c8202ff |
op_doi |
https://doi.org/10.1371/journal.pntd.0005084 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
10 |
container_issue |
11 |
container_start_page |
e0005084 |
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1766340196780998656 |