Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution

Bibliographic Details
Main Author: Carvalho, Henrique F.
Publication Date: 2015
Other Authors: Roque, Ana C. A., Iranzo, Olga, Branco, Ricardo Jorge Flores
Format: Article
Language: eng
Source: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Download full: http://hdl.handle.net/10362/36406
Summary: HC is holder of grant number SFRH/BD/90644/2012, OI grant number PTDC/QEQ-MED/2656/2012, RJFB grants number SFRH/BPD/69163/2010 and ERA-IB-2/0001/2013, ACAR grants number PTDC/EBB-BIO/118317/2010 and UID/Multi/04378/2013 from Fundacao para a Ciencia e a Tecnologia (http://www.fct.pt/)."
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spelling Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and EvolutionEvolution, MolecularMetalloproteasesModels, MolecularThermolysinComparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tHC is holder of grant number SFRH/BD/90644/2012, OI grant number PTDC/QEQ-MED/2656/2012, RJFB grants number SFRH/BPD/69163/2010 and ERA-IB-2/0001/2013, ACAR grants number PTDC/EBB-BIO/118317/2010 and UID/Multi/04378/2013 from Fundacao para a Ciencia e a Tecnologia (http://www.fct.pt/)."Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories. A close correspondence was obtained between modes derived from the coarse-grained model and the subspace of functionally-relevant motions observed experimentally, the later being shown to be encoded in the internal dynamics of the protein. This prompted the use of dynamics-based comparison methods that employ such coarse-grained models in a representative set of clan members, allowing for its quantitative description in terms of structural and dynamical variability. Although members show structural similarity, they nonetheless present distinct dynamical profiles, with no apparent correlation between structural and dynamical relatedness. However, previously unnoticed dynamical similarity was found between the relevant members Carboxypeptidase Pfu, Leishmanolysin, and Botulinum Neurotoxin Type A, despite sharing no structural similarity. Inspection of the respective alignments shows that dynamical similarity has a functional basis, namely the need for maintaining proper intermolecular interactions with the respective substrates. These results suggest that distinct selective pressure mechanisms act on metalloproteases at structural and dynamical levels through the course of their evolution. This work shows how new insights on metalloprotease function and evolution can be assessed with comparison schemes that incorporate information on protein dynamics. The integration of these newly developed tools, if applied to other protein families, can lead to more accurate and descriptive protein classification systems.Instituto de Tecnologia Química e Biológica António Xavier (ITQB)DQ - Departamento de QuímicaUCIBIO - Applied Molecular Biosciences UnitRUNCarvalho, Henrique F.Roque, Ana C. A.Iranzo, OlgaBranco, Ricardo Jorge Flores2018-05-10T22:04:28Z2015-09-232015-09-23T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/36406eng1932-6203PURE: 1374392https://doi.org/10.1371/journal.pone.0138118info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:19:47Zoai:run.unl.pt:10362/36406Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:30:28.164067Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
title Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
spellingShingle Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
Carvalho, Henrique F.
Evolution, Molecular
Metalloproteases
Models, Molecular
Thermolysin
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
title_short Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
title_full Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
title_fullStr Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
title_full_unstemmed Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
title_sort Comparison of the Internal Dynamics of Metalloproteases Provides New Insights on Their Function and Evolution
author Carvalho, Henrique F.
author_facet Carvalho, Henrique F.
Roque, Ana C. A.
Iranzo, Olga
Branco, Ricardo Jorge Flores
author_role author
author2 Roque, Ana C. A.
Iranzo, Olga
Branco, Ricardo Jorge Flores
author2_role author
author
author
dc.contributor.none.fl_str_mv Instituto de Tecnologia Química e Biológica António Xavier (ITQB)
DQ - Departamento de Química
UCIBIO - Applied Molecular Biosciences Unit
RUN
dc.contributor.author.fl_str_mv Carvalho, Henrique F.
Roque, Ana C. A.
Iranzo, Olga
Branco, Ricardo Jorge Flores
dc.subject.por.fl_str_mv Evolution, Molecular
Metalloproteases
Models, Molecular
Thermolysin
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
topic Evolution, Molecular
Metalloproteases
Models, Molecular
Thermolysin
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
description HC is holder of grant number SFRH/BD/90644/2012, OI grant number PTDC/QEQ-MED/2656/2012, RJFB grants number SFRH/BPD/69163/2010 and ERA-IB-2/0001/2013, ACAR grants number PTDC/EBB-BIO/118317/2010 and UID/Multi/04378/2013 from Fundacao para a Ciencia e a Tecnologia (http://www.fct.pt/)."
publishDate 2015
dc.date.none.fl_str_mv 2015-09-23
2015-09-23T00:00:00Z
2018-05-10T22:04:28Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/36406
url http://hdl.handle.net/10362/36406
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1932-6203
PURE: 1374392
https://doi.org/10.1371/journal.pone.0138118
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
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