Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition

Autores
Capece, Luciana; Estrin, Dario Ariel; Marti, Marcelo Adrian
Año de publicación
2008
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO) numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO induced breaking of the iron proximal histidine bond in the so called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came however from the elucidation of crystal structures for two different prokaryotic Heme NO Oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX, that complement these structural studies yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the áFâ1 loop and the áA-áC distal subdomain. The results from the sGC models also support this view and suggest a key role for the áFâ1 loop in the iron proximal histidine bond breaking process and therefore, in the sGC activation mechanism.
Fil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Marti, Marcelo Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
NO
molecular dynamics
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:11336/103060
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric TransitionCapece, LucianaEstrin, Dario ArielMarti, Marcelo AdrianNOmolecular dynamicshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO) numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO induced breaking of the iron proximal histidine bond in the so called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came however from the elucidation of crystal structures for two different prokaryotic Heme NO Oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX, that complement these structural studies yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the áFâ1 loop and the áA-áC distal subdomain. The results from the sGC models also support this view and suggest a key role for the áFâ1 loop in the iron proximal histidine bond breaking process and therefore, in the sGC activation mechanism.Fil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; ArgentinaFil: Marti, Marcelo Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaAmerican Chemical Society2008-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103060Capece, Luciana; Estrin, Dario Ariel; Marti, Marcelo Adrian; Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition; American Chemical Society; Biochemistry; 47; 36; 9-2008; 9416-94270006-2960CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/bi800682kinfo:eu-repo/semantics/altIdentifier/doi/10.1021/bi800682kinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:27:16Zoai:ri.conicet.gov.ar:11336/103060instacron: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:34982025-10-22 11:27:16.341CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
title Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
spellingShingle Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
Capece, Luciana
NO
molecular dynamics
title_short Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
title_full Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
title_fullStr Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
title_full_unstemmed Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
title_sort Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition
dc.creator.none.fl_str_mv Capece, Luciana
Estrin, Dario Ariel
Marti, Marcelo Adrian
author Capece, Luciana
author_facet Capece, Luciana
Estrin, Dario Ariel
Marti, Marcelo Adrian
author_role author
author2 Estrin, Dario Ariel
Marti, Marcelo Adrian
author2_role author
author
dc.subject.none.fl_str_mv NO
molecular dynamics
topic NO
molecular dynamics
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO) numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO induced breaking of the iron proximal histidine bond in the so called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came however from the elucidation of crystal structures for two different prokaryotic Heme NO Oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX, that complement these structural studies yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the áFâ1 loop and the áA-áC distal subdomain. The results from the sGC models also support this view and suggest a key role for the áFâ1 loop in the iron proximal histidine bond breaking process and therefore, in the sGC activation mechanism.
Fil: Capece, Luciana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Estrin, Dario Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química, Física de los Materiales, Medioambiente y Energía. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química, Física de los Materiales, Medioambiente y Energía; Argentina
Fil: Marti, Marcelo Adrian. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description Since the discovery of soluble guanylate cyclase (sGC) as the mammalian receptor for nitric oxide (NO) numerous studies have been performed in order to understand how sGC transduces the NO signal. However, the structural basis of sGC activation is still not completely elucidated. Spectroscopic and kinetic studies showed that the key step in the activation mechanism was the NO induced breaking of the iron proximal histidine bond in the so called 6c-NO to 5c-NO transition. The main breakthrough in the understanding of sGC activation mechanism came however from the elucidation of crystal structures for two different prokaryotic Heme NO Oxygen (HNOX) domains, which are homologues to the sGC heme domain. In this work we present computer simulation results of Thermoanaerobacter tencogensis HNOX, that complement these structural studies yielding molecular explanations to several poorly understood properties of these proteins. Specifically, our results explain the differential ligand binding patterns of the HNOX domains according to the nature of proximal and distal residues. We also show that the natural dynamics of these proteins is intimately related with the proposed conformational dependent activation process, which involves mainly the áFâ1 loop and the áA-áC distal subdomain. The results from the sGC models also support this view and suggest a key role for the áFâ1 loop in the iron proximal histidine bond breaking process and therefore, in the sGC activation mechanism.
publishDate 2008
dc.date.none.fl_str_mv 2008-09
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/11336/103060
Capece, Luciana; Estrin, Dario Ariel; Marti, Marcelo Adrian; Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition; American Chemical Society; Biochemistry; 47; 36; 9-2008; 9416-9427
0006-2960
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103060
identifier_str_mv Capece, Luciana; Estrin, Dario Ariel; Marti, Marcelo Adrian; Dynamical Characterization of the Heme NO Oxygen Binding (HNOX) Domain. Insight into Soluble Guanylate Cyclase Allosteric Transition; American Chemical Society; Biochemistry; 47; 36; 9-2008; 9416-9427
0006-2960
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/10.1021/bi800682k
info:eu-repo/semantics/altIdentifier/doi/10.1021/bi800682k
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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 12.982451

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