The pseudo-dimeric tyrosyl-tRNA synthetase of T. brucei aminoacylates cytosolic and mitochondrial tRNATyr and requires both monomeric units for activity

Käser, Sandro; Glauser, Isabelle; Rettig, Jochen; Schneider, André

doi:10.1016/j.molbiopara.2018.03.004

Cited by 4 publications

(3 citation statements)

References 19 publications

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“…Finally, it is known that TyrRS classically forms a homodimer and the binding-site for one molecule of tRNA Tyr straddles both subunits (32). In the case of trypanosomatids, our MSA confirms that TyrRS is a double-length enzyme that forms a pseudo-dimer, as previously observed for L. major and T. brucei TyrRSs (33,34). The analysis of the crystallographic structure of L. major TyrRS revealed that the C-terminal monomer is missing some catalytic residues specific of a class I aaRS (KMSKS replaced by ARAVL), and the N-terminal monomer has a 6 residue deletion that structurally affects its anticodon binding domain (33).…”

Section: Identification Of Sequence Peculiarities Of Trypanosomatids Aarsssupporting

confidence: 87%

Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids

Parrot

Moulinier

Bernard

et al. 2021

Journal of Biological Chemistry

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Identification Of Sequence Peculiarities Of Trypanosomatids Aarsssupporting

confidence: 87%

Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids

Parrot

Moulinier

Bernard

et al. 2021

Journal of Biological Chemistry

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“…Tb TyrRS, like Lm TyrRS, forms a pseudo-dimer and is capable of aminoacylating both mitochondrial as well as cytosolic tRNA Tyr . Furthermore, the deletion of 36 amino acid residues either from the N- or C-termini abolished the Tb TyrRS function, raising the question of what could be the possible role of these amino acid residues in its catalysis . Some of the previously proclaimed antiparasitic plant derivatives such as polyphenolic compounds and alkaloids have been shown to specifically target the active pocket of leishmanial TyrRS with the help of molecular docking analysis. , …”

Section: Research Accomplished On Trypanosomatid Aminoacyl Trna Synth...mentioning

confidence: 99%

Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites

Nasim

Qureshi

2023

ACS Omega

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The ensemble of aminoacyl tRNA synthetases is regarded as a key component of the protein translation machinery. With the progressive increase in structure-based studies on tRNA synthetase-ligand complexes, the detailed picture of these enzymes is becoming clear. Having known their critical role in deciphering the genetic code in a living system, they have always been chosen as one of the important targets for development of antimicrobial drugs. Later on, the role of aminoacyl tRNA synthetases (aaRSs) on the survivability of trypanosomatids has also been validated. It became evident through several gene knockout studies that targeting even one of these enzymes affected parasitic growth drastically. Such successful studies have inspired researchers to search for inhibitors that could specifically target trypanosomal aaRSs, and their never-ending efforts have provided fruitful results. Taking all such studies into consideration, these macromolecules of prime importance deserve further investigation for the development of drugs that cure spectrum of infections caused by trypanosomatids. In this review, we have compiled advancements of over a decade that have taken place in the pursuit of devising drugs by using trypanosomatid aaRSs as a major target of interest. Several of these inhibitors work on an exemplary low concentration range without posing any threat to the mammalian cells which is a very critical aspect of the drug discovery process. Advancements have been made in terms of using structural biology as an important tool to analyze the architecture of the trypanosomatids aaRSs and concoction of inhibitors with augmented specificities toward their targets. Some of the inhibitors that have been tested on other parasites successfully but their efficacy has so far not been validated against these trypanosomatids have also been appended.

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“…[13d,36] Thus, we would expect that these 17 aaRSs function in both cytosolic and mitochondrial translation. Indeed, it has been experimentally verified for the cytosolic and mitochondrial GlnRS, GluRS [37] and TyrRS activities, [38] that each are encoded by a single nuclear gene. Typically, most of a given trypanosomal aaRS resides in the cytosol and only a minor fraction is imported.…”

Section: Formation Of Sec-trna Secmentioning

confidence: 99%

tRNA Biology in Trypanosomes

Shikha¹,

Brogli²,

Schneider³

et al. 2019

Chimia

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Besides their medical importance, the parasitic protozoan Trypanosoma brucei and its relatives are experimentally highly accessible model systems for many cell biological processes. Trypanosomes are phylogenetically essentially unrelated to the popular model eukaryotes, such as yeast and animals, and thus show several unique features, many of which are connected to RNA. Here we review the tRNA biology of trypanosomes. Even though tRNAs were already discovered 60 years ago, owing to current technological advances in the field, research on tRNA biology has seen a Renaissance in recent years. First we discuss the extensive mitochondrial tRNA import process and the consequences it has for the parasite. Next we focus on trypanosomal aminoacyl-tRNA synthetases, some of which may be exploited as drug targets. Furthermore, we summarize what is known about trypanosomal tRNA modifications in both the cytosol and the mitochondrion. Finally, we provide an overview on the emerging field of tRNA-derived fragments and their possible function as translation regulators.

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The pseudo-dimeric tyrosyl-tRNA synthetase of T. brucei aminoacylates cytosolic and mitochondrial tRNATyr and requires both monomeric units for activity

Cited by 4 publications

References 19 publications

Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids

Peculiarities of aminoacyl-tRNA synthetases from trypanosomatids

Aminoacyl tRNA Synthetases: Implications of Structural Biology in Drug Development against Trypanosomatid Parasites

tRNA Biology in Trypanosomes

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