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An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase

Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in...

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Autores principales: Khan, Sameena, Garg, Ankur, Sharma, Arvind, Camacho, Noelia, Picchioni, Daria, Saint-Léger, Adélaïde, de Pouplana, Lluís Ribas, Yogavel, Manickam, Sharma, Amit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680381/
https://www.ncbi.nlm.nih.gov/pubmed/23776638
http://dx.doi.org/10.1371/journal.pone.0066224
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author Khan, Sameena
Garg, Ankur
Sharma, Arvind
Camacho, Noelia
Picchioni, Daria
Saint-Léger, Adélaïde
de Pouplana, Lluís Ribas
Yogavel, Manickam
Sharma, Amit
author_facet Khan, Sameena
Garg, Ankur
Sharma, Arvind
Camacho, Noelia
Picchioni, Daria
Saint-Léger, Adélaïde
de Pouplana, Lluís Ribas
Yogavel, Manickam
Sharma, Amit
author_sort Khan, Sameena
collection PubMed
description Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in complex with L-tryptophan. Confocal microscopy-based localization data suggest cytoplasmic residency of this protein. Pf-WRS has an unusual N-terminal extension of AlaX-like domain (AXD) along with linker regions which together seem vital for enzymatic activity and tRNA binding. Pf-WRS is not proteolytically processed in the parasites and therefore AXD likely provides tRNA binding capability rather than editing activity. The N-terminal domain containing AXD and linker region is monomeric and would result in an unusual overall architecture for Pf-WRS where the dimeric catalytic domains have monomeric AXDs on either side. Our PDB-wide comparative analyses of 47 WRS crystal structures also provide new mechanistic insights into this enzyme family in context conserved KMSKS loop conformations.
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spelling pubmed-36803812013-06-17 An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase Khan, Sameena Garg, Ankur Sharma, Arvind Camacho, Noelia Picchioni, Daria Saint-Léger, Adélaïde de Pouplana, Lluís Ribas Yogavel, Manickam Sharma, Amit PLoS One Research Article Specific activation of amino acids by aminoacyl-tRNA synthetases (aaRSs) is essential for maintaining fidelity during protein translation. Here, we present crystal structure of malaria parasite Plasmodium falciparum tryptophanyl-tRNA synthetase (Pf-WRS) catalytic domain (AAD) at 2.6 Å resolution in complex with L-tryptophan. Confocal microscopy-based localization data suggest cytoplasmic residency of this protein. Pf-WRS has an unusual N-terminal extension of AlaX-like domain (AXD) along with linker regions which together seem vital for enzymatic activity and tRNA binding. Pf-WRS is not proteolytically processed in the parasites and therefore AXD likely provides tRNA binding capability rather than editing activity. The N-terminal domain containing AXD and linker region is monomeric and would result in an unusual overall architecture for Pf-WRS where the dimeric catalytic domains have monomeric AXDs on either side. Our PDB-wide comparative analyses of 47 WRS crystal structures also provide new mechanistic insights into this enzyme family in context conserved KMSKS loop conformations. Public Library of Science 2013-06-12 /pmc/articles/PMC3680381/ /pubmed/23776638 http://dx.doi.org/10.1371/journal.pone.0066224 Text en © 2013 Khan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Khan, Sameena
Garg, Ankur
Sharma, Arvind
Camacho, Noelia
Picchioni, Daria
Saint-Léger, Adélaïde
de Pouplana, Lluís Ribas
Yogavel, Manickam
Sharma, Amit
An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title_full An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title_fullStr An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title_full_unstemmed An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title_short An Appended Domain Results in an Unusual Architecture for Malaria Parasite Tryptophanyl-tRNA Synthetase
title_sort appended domain results in an unusual architecture for malaria parasite tryptophanyl-trna synthetase
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680381/
https://www.ncbi.nlm.nih.gov/pubmed/23776638
http://dx.doi.org/10.1371/journal.pone.0066224
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