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Ligand-driven conformational changes of MurD visualized by paramagnetic NMR

Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step to regulate their function. However, the detailed mechanisms of such dynamic regulation of the functional processes are poorly...

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Autores principales: Saio, Tomohide, Ogura, Kenji, Kumeta, Hiroyuki, Kobashigawa, Yoshihiro, Shimizu, Kazumi, Yokochi, Masashi, Kodama, Kota, Yamaguchi, Hiroto, Tsujishita, Hideki, Inagaki, Fuyuhiko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652230/
https://www.ncbi.nlm.nih.gov/pubmed/26582338
http://dx.doi.org/10.1038/srep16685
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author Saio, Tomohide
Ogura, Kenji
Kumeta, Hiroyuki
Kobashigawa, Yoshihiro
Shimizu, Kazumi
Yokochi, Masashi
Kodama, Kota
Yamaguchi, Hiroto
Tsujishita, Hideki
Inagaki, Fuyuhiko
author_facet Saio, Tomohide
Ogura, Kenji
Kumeta, Hiroyuki
Kobashigawa, Yoshihiro
Shimizu, Kazumi
Yokochi, Masashi
Kodama, Kota
Yamaguchi, Hiroto
Tsujishita, Hideki
Inagaki, Fuyuhiko
author_sort Saio, Tomohide
collection PubMed
description Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step to regulate their function. However, the detailed mechanisms of such dynamic regulation of the functional processes are poorly understood because of the lack of an efficient tool. We here demonstrate detailed characterization of conformational changes of MurD, a 47 kDa protein enzyme consisting of three domains, by the use of solution NMR equipped with paramagnetic lanthanide probe. Quantitative analysis of pseudocontact shifts has identified a novel conformational state of MurD, named semi-closed conformation, which is found to be the key to understand how MurD regulates the binding of the ligands. The modulation of the affinity coupled with conformational changes accentuates the importance of conformational state to be evaluated in drug design.
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spelling pubmed-46522302015-11-24 Ligand-driven conformational changes of MurD visualized by paramagnetic NMR Saio, Tomohide Ogura, Kenji Kumeta, Hiroyuki Kobashigawa, Yoshihiro Shimizu, Kazumi Yokochi, Masashi Kodama, Kota Yamaguchi, Hiroto Tsujishita, Hideki Inagaki, Fuyuhiko Sci Rep Article Proteins, especially multi-domain proteins, often undergo drastic conformational changes upon binding to ligands or by post-translational modifications, which is a key step to regulate their function. However, the detailed mechanisms of such dynamic regulation of the functional processes are poorly understood because of the lack of an efficient tool. We here demonstrate detailed characterization of conformational changes of MurD, a 47 kDa protein enzyme consisting of three domains, by the use of solution NMR equipped with paramagnetic lanthanide probe. Quantitative analysis of pseudocontact shifts has identified a novel conformational state of MurD, named semi-closed conformation, which is found to be the key to understand how MurD regulates the binding of the ligands. The modulation of the affinity coupled with conformational changes accentuates the importance of conformational state to be evaluated in drug design. Nature Publishing Group 2015-11-19 /pmc/articles/PMC4652230/ /pubmed/26582338 http://dx.doi.org/10.1038/srep16685 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Saio, Tomohide
Ogura, Kenji
Kumeta, Hiroyuki
Kobashigawa, Yoshihiro
Shimizu, Kazumi
Yokochi, Masashi
Kodama, Kota
Yamaguchi, Hiroto
Tsujishita, Hideki
Inagaki, Fuyuhiko
Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title_full Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title_fullStr Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title_full_unstemmed Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title_short Ligand-driven conformational changes of MurD visualized by paramagnetic NMR
title_sort ligand-driven conformational changes of murd visualized by paramagnetic nmr
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4652230/
https://www.ncbi.nlm.nih.gov/pubmed/26582338
http://dx.doi.org/10.1038/srep16685
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