The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target

Abstract Flexibility is a feature intimately related to protein function, since conformational changes can be used to describe environmental changes, chemical modifications, protein-protein and protein-ligand interactions. In this study, we have investigated the influence of the quaternary structure...

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Autores principales:	Renata Fioravanti Tarabini, Luís Fernando Saraiva Macedo Timmers, Carlos Eduardo Sequeiros-Borja, Osmar Norberto de Souza
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2aa7a22fd26e4c11bc04ecb42ed434a5
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spelling	oai:doaj.org-article:2aa7a22fd26e4c11bc04ecb42ed434a52021-12-02T15:09:22ZThe importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target10.1038/s41598-019-50213-02045-2322https://doaj.org/article/2aa7a22fd26e4c11bc04ecb42ed434a52019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-50213-0https://doaj.org/toc/2045-2322Abstract Flexibility is a feature intimately related to protein function, since conformational changes can be used to describe environmental changes, chemical modifications, protein-protein and protein-ligand interactions. In this study, we have investigated the influence of the quaternary structure of 2-trans-enoyl-ACP (CoA) reductase or InhA, from Mycobacterium tuberculosis, to its flexibility. We carried out classical molecular dynamics simulations using monomeric and tetrameric forms to elucidate the enzyme’s flexibility. Overall, we observed statistically significant differences between conformational ensembles of tertiary and quaternary structures. In addition, the enzyme’s binding site is the most affected region, reinforcing the importance of the quaternary structure to evaluate the binding affinity of small molecules, as well as the effect of single point mutations to InhA protein dynamics.Renata Fioravanti TarabiniLuís Fernando Saraiva Macedo TimmersCarlos Eduardo Sequeiros-BorjaOsmar Norberto de SouzaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Renata Fioravanti Tarabini Luís Fernando Saraiva Macedo Timmers Carlos Eduardo Sequeiros-Borja Osmar Norberto de Souza The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
description	Abstract Flexibility is a feature intimately related to protein function, since conformational changes can be used to describe environmental changes, chemical modifications, protein-protein and protein-ligand interactions. In this study, we have investigated the influence of the quaternary structure of 2-trans-enoyl-ACP (CoA) reductase or InhA, from Mycobacterium tuberculosis, to its flexibility. We carried out classical molecular dynamics simulations using monomeric and tetrameric forms to elucidate the enzyme’s flexibility. Overall, we observed statistically significant differences between conformational ensembles of tertiary and quaternary structures. In addition, the enzyme’s binding site is the most affected region, reinforcing the importance of the quaternary structure to evaluate the binding affinity of small molecules, as well as the effect of single point mutations to InhA protein dynamics.
format	article
author	Renata Fioravanti Tarabini Luís Fernando Saraiva Macedo Timmers Carlos Eduardo Sequeiros-Borja Osmar Norberto de Souza
author_facet	Renata Fioravanti Tarabini Luís Fernando Saraiva Macedo Timmers Carlos Eduardo Sequeiros-Borja Osmar Norberto de Souza
author_sort	Renata Fioravanti Tarabini
title	The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
title_short	The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
title_full	The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
title_fullStr	The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
title_full_unstemmed	The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target
title_sort	importance of the quaternary structure to represent conformational ensembles of the major mycobacterium tuberculosis drug target
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/2aa7a22fd26e4c11bc04ecb42ed434a5
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The importance of the quaternary structure to represent conformational ensembles of the major Mycobacterium tuberculosis drug target

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