Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes

Autores
Jack, Benjamin R.; Meyer, Austin G.; Echave, Julián; Wilke, Claus O.
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.
Fil: Jack, Benjamin R.. University of Texas at Austin; Estados Unidos
Fil: Meyer, Austin G.. University of Texas at Austin; Estados Unidos
Fil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilke, Claus O.. University of Texas at Austin; Estados Unidos
Materia
Protein
Evolution
Functional
Constraints
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:11336/45007

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network_name_str CONICET Digital (CONICET)
spelling Functional Sites Induce Long-Range Evolutionary Constraints in EnzymesJack, Benjamin R.Meyer, Austin G.Echave, JuliánWilke, Claus O.ProteinEvolutionFunctionalConstraintshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.Fil: Jack, Benjamin R.. University of Texas at Austin; Estados UnidosFil: Meyer, Austin G.. University of Texas at Austin; Estados UnidosFil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Wilke, Claus O.. University of Texas at Austin; Estados UnidosPublic Library of Science2016-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/zipapplication/pdfhttp://hdl.handle.net/11336/45007Jack, Benjamin R.; Meyer, Austin G.; Echave, Julián; Wilke, Claus O.; Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes; Public Library of Science; PLoS Biology; 14; 5; 5-2016; 1-23; e10024521545-7885CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.1002452info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002452info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:39:06Zoai:ri.conicet.gov.ar:11336/45007instacron: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 09:39:06.78CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
title Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
spellingShingle Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
Jack, Benjamin R.
Protein
Evolution
Functional
Constraints
title_short Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
title_full Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
title_fullStr Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
title_full_unstemmed Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
title_sort Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes
dc.creator.none.fl_str_mv Jack, Benjamin R.
Meyer, Austin G.
Echave, Julián
Wilke, Claus O.
author Jack, Benjamin R.
author_facet Jack, Benjamin R.
Meyer, Austin G.
Echave, Julián
Wilke, Claus O.
author_role author
author2 Meyer, Austin G.
Echave, Julián
Wilke, Claus O.
author2_role author
author
author
dc.subject.none.fl_str_mv Protein
Evolution
Functional
Constraints
topic Protein
Evolution
Functional
Constraints
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.
Fil: Jack, Benjamin R.. University of Texas at Austin; Estados Unidos
Fil: Meyer, Austin G.. University of Texas at Austin; Estados Unidos
Fil: Echave, Julián. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Wilke, Claus O.. University of Texas at Austin; Estados Unidos
description Functional residues in proteins tend to be highly conserved over evolutionary time. However, to what extent functional sites impose evolutionary constraints on nearby or even more distant residues is not known. Here, we report pervasive conservation gradients toward catalytic residues in a dataset of 524 distinct enzymes: evolutionary conservation decreases approximately linearly with increasing distance to the nearest catalytic residue in the protein structure. This trend encompasses, on average, 80% of the residues in any enzyme, and it is independent of known structural constraints on protein evolution such as residue packing or solvent accessibility. Further, the trend exists in both monomeric and multimeric enzymes and irrespective of enzyme size and/or location of the active site in the enzyme structure. By contrast, sites in protein–protein interfaces, unlike catalytic residues, are only weakly conserved and induce only minor rate gradients. In aggregate, these observations show that functional sites, and in particular catalytic residues, induce long-range evolutionary constraints in enzymes.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
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/11336/45007
Jack, Benjamin R.; Meyer, Austin G.; Echave, Julián; Wilke, Claus O.; Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes; Public Library of Science; PLoS Biology; 14; 5; 5-2016; 1-23; e1002452
1545-7885
CONICET Digital
CONICET
url http://hdl.handle.net/11336/45007
identifier_str_mv Jack, Benjamin R.; Meyer, Austin G.; Echave, Julián; Wilke, Claus O.; Functional Sites Induce Long-Range Evolutionary Constraints in Enzymes; Public Library of Science; PLoS Biology; 14; 5; 5-2016; 1-23; e1002452
1545-7885
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1371/journal.pbio.1002452
info:eu-repo/semantics/altIdentifier/url/http://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002452
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/zip
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
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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