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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/45007
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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 |
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reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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13.070432 |