Local frustration around enzyme active sites

Autores
Freiberger, Maria Ines; Guzovsky, Ana Brenda; Wolynes, Peter G.; Parra, Rodrigo Gonzalo; Ferreiro, Diego
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
Fil: Freiberger, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Entre Ríos; Argentina
Fil: Guzovsky, Ana Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
Fil: Parra, Rodrigo Gonzalo. Universidad Nacional de Entre Ríos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Materia
BIOINFORMATICS
CATALYTIC SITES
EVOLUTION
LOCAL FRUSTRATION
PROTEIN ENZYMES
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/121823
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/121823
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Local frustration around enzyme active sitesFreiberger, Maria InesGuzovsky, Ana BrendaWolynes, Peter G.Parra, Rodrigo GonzaloFerreiro, DiegoBIOINFORMATICSCATALYTIC SITESEVOLUTIONLOCAL FRUSTRATIONPROTEIN ENZYMEShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.Fil: Freiberger, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Entre Ríos; ArgentinaFil: Guzovsky, Ana Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Wolynes, Peter G.. Rice University; Estados UnidosFil: Parra, Rodrigo Gonzalo. Universidad Nacional de Entre Ríos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaNational Academy of Sciences2019-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/121823Freiberger, Maria Ines; Guzovsky, Ana Brenda; Wolynes, Peter G.; Parra, Rodrigo Gonzalo; Ferreiro, Diego; Local frustration around enzyme active sites; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 10; 2-2019; 4037-40430027-84241091-6490CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1819859116info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/10/4037info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:25:52Zoai:ri.conicet.gov.ar:11336/121823instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:25:52.697CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Local frustration around enzyme active sites
title Local frustration around enzyme active sites
spellingShingle Local frustration around enzyme active sites
Freiberger, Maria Ines
BIOINFORMATICS
CATALYTIC SITES
EVOLUTION
LOCAL FRUSTRATION
PROTEIN ENZYMES
title_short Local frustration around enzyme active sites
title_full Local frustration around enzyme active sites
title_fullStr Local frustration around enzyme active sites
title_full_unstemmed Local frustration around enzyme active sites
title_sort Local frustration around enzyme active sites
dc.creator.none.fl_str_mv Freiberger, Maria Ines
Guzovsky, Ana Brenda
Wolynes, Peter G.
Parra, Rodrigo Gonzalo
Ferreiro, Diego
author Freiberger, Maria Ines
author_facet Freiberger, Maria Ines
Guzovsky, Ana Brenda
Wolynes, Peter G.
Parra, Rodrigo Gonzalo
Ferreiro, Diego
author_role author
author2 Guzovsky, Ana Brenda
Wolynes, Peter G.
Parra, Rodrigo Gonzalo
Ferreiro, Diego
author2_role author
author
author
author
dc.subject.none.fl_str_mv BIOINFORMATICS
CATALYTIC SITES
EVOLUTION
LOCAL FRUSTRATION
PROTEIN ENZYMES
topic BIOINFORMATICS
CATALYTIC SITES
EVOLUTION
LOCAL FRUSTRATION
PROTEIN ENZYMES
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
Fil: Freiberger, Maria Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina. Universidad Nacional de Entre Ríos; Argentina
Fil: Guzovsky, Ana Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Wolynes, Peter G.. Rice University; Estados Unidos
Fil: Parra, Rodrigo Gonzalo. Universidad Nacional de Entre Ríos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Ferreiro, Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
description Conflicting biological goals often meet in the specification of protein sequences for structure and function. Overall, strong energetic conflicts are minimized in folded native states according to the principle of minimal frustration, so that a sequence can spontaneously fold, but local violations of this principle open up the possibility to encode the complex energy landscapes that are required for active biological functions. We survey the local energetic frustration patterns of all protein enzymes with known structures and experimentally annotated catalytic residues. In agreement with previous hypotheses, the catalytic sites themselves are often highly frustrated regardless of the protein oligomeric state, overall topology, and enzymatic class. At the same time a secondary shell of more weakly frustrated interactions surrounds the catalytic site itself. We evaluate the conservation of these energetic signatures in various family members of major enzyme classes, showing that local frustration is evolutionarily more conserved than the primary structure itself.
publishDate 2019
dc.date.none.fl_str_mv 2019-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/121823
Freiberger, Maria Ines; Guzovsky, Ana Brenda; Wolynes, Peter G.; Parra, Rodrigo Gonzalo; Ferreiro, Diego; Local frustration around enzyme active sites; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 10; 2-2019; 4037-4043
0027-8424
1091-6490
CONICET Digital
CONICET
url http://hdl.handle.net/11336/121823
identifier_str_mv Freiberger, Maria Ines; Guzovsky, Ana Brenda; Wolynes, Peter G.; Parra, Rodrigo Gonzalo; Ferreiro, Diego; Local frustration around enzyme active sites; National Academy of Sciences; Proceedings of the National Academy of Sciences of The United States of America; 116; 10; 2-2019; 4037-4043
0027-8424
1091-6490
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1073/pnas.1819859116
info:eu-repo/semantics/altIdentifier/url/https://www.pnas.org/content/116/10/4037
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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