Packing defects functionalize soluble proteins

Autores
Fernandez, Ariel
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This work explores the participation of protein packing defects, the so-called dehydrons, in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton-displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron-generating mutations.2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; Argentina
Materia
Molecular Biophysics
Dehydron
Enzyme
Biomolecular Interface
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:11336/18950
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/18950
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Packing defects functionalize soluble proteinsFernandez, ArielMolecular BiophysicsDehydronEnzymeBiomolecular Interfacehttps://purl.org/becyt/ford/1.3https://purl.org/becyt/ford/1This work explores the participation of protein packing defects, the so-called dehydrons, in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton-displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron-generating mutations.2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; ArgentinaWiley2015-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/18950Fernandez, Ariel; Packing defects functionalize soluble proteins; Wiley; FEBS Letters; 589; 9; 3-2015; 967-9730014-5793CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.03.002/abstractinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.febslet.2015.03.002info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014579315001404info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:55:52Zoai:ri.conicet.gov.ar:11336/18950instacron: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 09:55:52.35CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Packing defects functionalize soluble proteins
title Packing defects functionalize soluble proteins
spellingShingle Packing defects functionalize soluble proteins
Fernandez, Ariel
Molecular Biophysics
Dehydron
Enzyme
Biomolecular Interface
title_short Packing defects functionalize soluble proteins
title_full Packing defects functionalize soluble proteins
title_fullStr Packing defects functionalize soluble proteins
title_full_unstemmed Packing defects functionalize soluble proteins
title_sort Packing defects functionalize soluble proteins
dc.creator.none.fl_str_mv Fernandez, Ariel
author Fernandez, Ariel
author_facet Fernandez, Ariel
author_role author
dc.subject.none.fl_str_mv Molecular Biophysics
Dehydron
Enzyme
Biomolecular Interface
topic Molecular Biophysics
Dehydron
Enzyme
Biomolecular Interface
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.3
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv This work explores the participation of protein packing defects, the so-called dehydrons, in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton-displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron-generating mutations.2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Fil: Fernandez, Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Saavedra 15. Instituto Argentino de Matemática Alberto Calderon; Argentina
description This work explores the participation of protein packing defects, the so-called dehydrons, in biochemical events. We delineate the enabling role of dehydrons as activators of nucleophilic groups. This activation results from the induction of chemical basicity in interfacial water molecules, promoting deprotonation of adjacent nucleophiles. Through multiple steering molecular dynamics with pulling along the proton-displacement coordinate, we show that nucleophilic groups are functionally enabled by nearby dehydrons that promote proton transference. The computations are validated against experimentally determined pKa decreases at functional sites and biochemical probes of deregulated catalytic activity arising from dehydron-generating mutations.2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
publishDate 2015
dc.date.none.fl_str_mv 2015-03
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/11336/18950
Fernandez, Ariel; Packing defects functionalize soluble proteins; Wiley; FEBS Letters; 589; 9; 3-2015; 967-973
0014-5793
CONICET Digital
CONICET
url http://hdl.handle.net/11336/18950
identifier_str_mv Fernandez, Ariel; Packing defects functionalize soluble proteins; Wiley; FEBS Letters; 589; 9; 3-2015; 967-973
0014-5793
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://onlinelibrary.wiley.com/doi/10.1016/j.febslet.2015.03.002/abstract
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.febslet.2015.03.002
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0014579315001404
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 Wiley
publisher.none.fl_str_mv Wiley
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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