Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms

Abstract Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, a...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Spencer O. Moen, Thomas E. Edwards, David M. Dranow, Matthew C. Clifton, Banumathi Sankaran, Wesley C. Van Voorhis, Amit Sharma, Colin Manoil, Bart L. Staker, Peter J. Myler, Donald D. Lorimer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/514875561f484af5b0d951c78c79f7d3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:514875561f484af5b0d951c78c79f7d3
record_format	dspace
spelling	oai:doaj.org-article:514875561f484af5b0d951c78c79f7d32021-12-02T12:32:27ZLigand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms10.1038/s41598-017-00367-62045-2322https://doaj.org/article/514875561f484af5b0d951c78c79f7d32017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00367-6https://doaj.org/toc/2045-2322Abstract Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline. Here we investigate thirty-one aminoacyl-tRNA synthetases from infectious disease organisms by co-crystallization in the presence of their cognate amino acid, ATP, and/or inhibitors. Crystal structures were determined for a CysRS from Borrelia burgdorferi bound to AMP, GluRS from Borrelia burgdorferi and Burkholderia thailandensis bound to glutamic acid, a TrpRS from the eukaryotic pathogen Encephalitozoon cuniculi bound to tryptophan, a HisRS from Burkholderia thailandensis bound to histidine, and a LysRS from Burkholderia thailandensis bound to lysine. Thus, the presence of ligands may promote aaRS crystallization and structure determination. Comparison with homologous structures shows conformational flexibility that appears to be a recurring theme with this enzyme class.Spencer O. MoenThomas E. EdwardsDavid M. DranowMatthew C. CliftonBanumathi SankaranWesley C. Van VoorhisAmit SharmaColin ManoilBart L. StakerPeter J. MylerDonald D. LorimerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-10 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Spencer O. Moen Thomas E. Edwards David M. Dranow Matthew C. Clifton Banumathi Sankaran Wesley C. Van Voorhis Amit Sharma Colin Manoil Bart L. Staker Peter J. Myler Donald D. Lorimer Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
description	Abstract Aminoacyl-tRNA synthetases (aaRSs) charge tRNAs with their cognate amino acid, an essential precursor step to loading of charged tRNAs onto the ribosome and addition of the amino acid to the growing polypeptide chain during protein synthesis. Because of this important biological function, aminoacyl-tRNA synthetases have been the focus of anti-infective drug development efforts and two aaRS inhibitors have been approved as drugs. Several researchers in the scientific community requested aminoacyl-tRNA synthetases to be targeted in the Seattle Structural Genomics Center for Infectious Disease (SSGCID) structure determination pipeline. Here we investigate thirty-one aminoacyl-tRNA synthetases from infectious disease organisms by co-crystallization in the presence of their cognate amino acid, ATP, and/or inhibitors. Crystal structures were determined for a CysRS from Borrelia burgdorferi bound to AMP, GluRS from Borrelia burgdorferi and Burkholderia thailandensis bound to glutamic acid, a TrpRS from the eukaryotic pathogen Encephalitozoon cuniculi bound to tryptophan, a HisRS from Burkholderia thailandensis bound to histidine, and a LysRS from Burkholderia thailandensis bound to lysine. Thus, the presence of ligands may promote aaRS crystallization and structure determination. Comparison with homologous structures shows conformational flexibility that appears to be a recurring theme with this enzyme class.
format	article
author	Spencer O. Moen Thomas E. Edwards David M. Dranow Matthew C. Clifton Banumathi Sankaran Wesley C. Van Voorhis Amit Sharma Colin Manoil Bart L. Staker Peter J. Myler Donald D. Lorimer
author_facet	Spencer O. Moen Thomas E. Edwards David M. Dranow Matthew C. Clifton Banumathi Sankaran Wesley C. Van Voorhis Amit Sharma Colin Manoil Bart L. Staker Peter J. Myler Donald D. Lorimer
author_sort	Spencer O. Moen
title	Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
title_short	Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
title_full	Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
title_fullStr	Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
title_full_unstemmed	Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms
title_sort	ligand co-crystallization of aminoacyl-trna synthetases from infectious disease organisms
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/514875561f484af5b0d951c78c79f7d3
work_keys_str_mv	AT spenceromoen ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT thomaseedwards ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT davidmdranow ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT matthewcclifton ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT banumathisankaran ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT wesleycvanvoorhis ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT amitsharma ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT colinmanoil ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT bartlstaker ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT peterjmyler ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms AT donalddlorimer ligandcocrystallizationofaminoacyltrnasynthetasesfrominfectiousdiseaseorganisms
_version_	1718394034635931648

Ligand co-crystallization of aminoacyl-tRNA synthetases from infectious disease organisms

Ejemplares similares