Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study
Abstract Background Treatment of parasitic diseases has been challenging due to evolution of drug resistant parasites, and thus there is need to identify new class of drugs and drug targets. Protein translation is important for survival of malarial parasite, Plasmodium, and the pathway is present in...
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ftdoajarticles:oai:doaj.org/article:942fdcd7d98c4f42b50daf61ff481e52 2023-05-15T15:14:53+02:00 Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study Dorothy Wavinya Nyamai Özlem Tastan Bishop 2019-02-01T00:00:00Z https://doi.org/10.1186/s12936-019-2665-6 https://doaj.org/article/942fdcd7d98c4f42b50daf61ff481e52 EN eng BMC http://link.springer.com/article/10.1186/s12936-019-2665-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2665-6 1475-2875 https://doaj.org/article/942fdcd7d98c4f42b50daf61ff481e52 Malaria Journal, Vol 18, Iss 1, Pp 1-27 (2019) Aminoacyl tRNA synthetases Motif analysis Phylogenetic tree calculations Homology modelling Allosteric site Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2019 ftdoajarticles https://doi.org/10.1186/s12936-019-2665-6 2022-12-31T08:44:41Z Abstract Background Treatment of parasitic diseases has been challenging due to evolution of drug resistant parasites, and thus there is need to identify new class of drugs and drug targets. Protein translation is important for survival of malarial parasite, Plasmodium, and the pathway is present in all of its life cycle stages. Aminoacyl tRNA synthetases are primary enzymes in protein translation as they catalyse amino acid addition to the cognate tRNA. This study sought to understand differences between Plasmodium and human aminoacyl tRNA synthetases through bioinformatics analysis. Methods Plasmodium berghei, Plasmodium falciparum, Plasmodium fragile, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, Plasmodium yoelii and human aminoacyl tRNA synthetase sequences were retrieved from UniProt database and grouped into 20 families based on amino acid specificity. These families were further divided into two classes. Both families and classes were analysed. Motif discovery was carried out using the MEME software, sequence identity calculation was done using an in-house Python script, multiple sequence alignments were performed using PROMALS3D and TCOFFEE tools, and phylogenetic tree calculations were performed using MEGA vs 7.0 tool. Possible alternative binding sites were predicted using FTMap webserver and SiteMap tool. Results Motif discovery revealed Plasmodium-specific motifs while phylogenetic tree calculations showed that Plasmodium proteins have different evolutionary history to the human homologues. Human aaRSs sequences showed low sequence identity (below 40%) compared to Plasmodium sequences. Prediction of alternative binding sites revealed potential druggable sites in PfArgRS, PfMetRS and PfProRS at regions that are weakly conserved when compared to the human homologues. Multiple sequence analysis, motif discovery, pairwise sequence identity calculations and phylogenetic tree analysis showed significant differences between parasite and human aaRSs proteins despite ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 18 1 |
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ftdoajarticles |
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English |
topic |
Aminoacyl tRNA synthetases Motif analysis Phylogenetic tree calculations Homology modelling Allosteric site Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
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Aminoacyl tRNA synthetases Motif analysis Phylogenetic tree calculations Homology modelling Allosteric site Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Dorothy Wavinya Nyamai Özlem Tastan Bishop Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
topic_facet |
Aminoacyl tRNA synthetases Motif analysis Phylogenetic tree calculations Homology modelling Allosteric site Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Treatment of parasitic diseases has been challenging due to evolution of drug resistant parasites, and thus there is need to identify new class of drugs and drug targets. Protein translation is important for survival of malarial parasite, Plasmodium, and the pathway is present in all of its life cycle stages. Aminoacyl tRNA synthetases are primary enzymes in protein translation as they catalyse amino acid addition to the cognate tRNA. This study sought to understand differences between Plasmodium and human aminoacyl tRNA synthetases through bioinformatics analysis. Methods Plasmodium berghei, Plasmodium falciparum, Plasmodium fragile, Plasmodium knowlesi, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax, Plasmodium yoelii and human aminoacyl tRNA synthetase sequences were retrieved from UniProt database and grouped into 20 families based on amino acid specificity. These families were further divided into two classes. Both families and classes were analysed. Motif discovery was carried out using the MEME software, sequence identity calculation was done using an in-house Python script, multiple sequence alignments were performed using PROMALS3D and TCOFFEE tools, and phylogenetic tree calculations were performed using MEGA vs 7.0 tool. Possible alternative binding sites were predicted using FTMap webserver and SiteMap tool. Results Motif discovery revealed Plasmodium-specific motifs while phylogenetic tree calculations showed that Plasmodium proteins have different evolutionary history to the human homologues. Human aaRSs sequences showed low sequence identity (below 40%) compared to Plasmodium sequences. Prediction of alternative binding sites revealed potential druggable sites in PfArgRS, PfMetRS and PfProRS at regions that are weakly conserved when compared to the human homologues. Multiple sequence analysis, motif discovery, pairwise sequence identity calculations and phylogenetic tree analysis showed significant differences between parasite and human aaRSs proteins despite ... |
format |
Article in Journal/Newspaper |
author |
Dorothy Wavinya Nyamai Özlem Tastan Bishop |
author_facet |
Dorothy Wavinya Nyamai Özlem Tastan Bishop |
author_sort |
Dorothy Wavinya Nyamai |
title |
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
title_short |
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
title_full |
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
title_fullStr |
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
title_full_unstemmed |
Aminoacyl tRNA synthetases as malarial drug targets: a comparative bioinformatics study |
title_sort |
aminoacyl trna synthetases as malarial drug targets: a comparative bioinformatics study |
publisher |
BMC |
publishDate |
2019 |
url |
https://doi.org/10.1186/s12936-019-2665-6 https://doaj.org/article/942fdcd7d98c4f42b50daf61ff481e52 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 18, Iss 1, Pp 1-27 (2019) |
op_relation |
http://link.springer.com/article/10.1186/s12936-019-2665-6 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-019-2665-6 1475-2875 https://doaj.org/article/942fdcd7d98c4f42b50daf61ff481e52 |
op_doi |
https://doi.org/10.1186/s12936-019-2665-6 |
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Malaria Journal |
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18 |
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1 |
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1766345289292054528 |