Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis

Truncated hemoglobin-N is believed to constitute a defense mechanism of Mycobacterium tuberculosis against NO produced by macrophages, which is converted to the harmless nitrate anion. This process is catalyzed very efficiently, as the enzyme activity is limited by ligand diffusion. By using extende...

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Detalles Bibliográficos
Autores: Bidon Chanal, Axel, Marti, Marcelo Adrian, Estrin, Dario Ariel, Luque, Javier F.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/103134
Acceso en línea:http://hdl.handle.net/11336/103134
Access Level:acceso abierto
Palabra clave:truncated hemoglobin
molecular dynamics
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
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network_acronym_str AR
network_name_str Argentina
repository_id_str
dc.title.none.fl_str_mv Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
title Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
spellingShingle Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
Bidon Chanal, Axel
truncated hemoglobin
molecular dynamics
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
title_short Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
title_full Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
title_fullStr Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
title_full_unstemmed Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
title_sort Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis
dc.creator.none.fl_str_mv Bidon Chanal, Axel
Marti, Marcelo Adrian
Estrin, Dario Ariel
Luque, Javier F.
author Bidon Chanal, Axel
author_facet Bidon Chanal, Axel
Marti, Marcelo Adrian
Estrin, Dario Ariel
Luque, Javier F.
author_role author
author2 Marti, Marcelo Adrian
Estrin, Dario Ariel
Luque, Javier F.
author2_role author
author
author
dc.subject.none.fl_str_mv truncated hemoglobin
molecular dynamics
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
topic truncated hemoglobin
molecular dynamics
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
description Truncated hemoglobin-N is believed to constitute a defense mechanism of Mycobacterium tuberculosis against NO produced by macrophages, which is converted to the harmless nitrate anion. This process is catalyzed very efficiently, as the enzyme activity is limited by ligand diffusion. By using extended molecular dynamics simulations we explore the mechanism that regulates ligand diffusion and, particularly, the role played by residues that assist binding of O2 to the heme group. Our data strongly support the hypothesis that the access of NO to the heme cavity is dynamically regulated by the TyrB10-GlnE11 pair, which acts as a molecular switch that controls opening of the ligand diffusion tunnel. Binding of O2 to the heme group triggers local conformational changes in the TyrB10-GlnE11 pair, which favor opening of the PheE15 gate residue through global changes in the essential motions of the protein skeleton. The complex pattern of conformational changes triggered upon O2 binding is drastically altered in the GlnE11fAla and TyrB10fPhe mutants, which justifies the poor enzymatic activity observed experimentally for the TyrB10fPhe form. The results support a molecular mechanism evolved to ensure access of NO to the heme cavity in the oxygenated form of the protein, which should warrant survival of the microorganism under stress conditions.
publishDate 2007
dc.date.none.fl_str_mv 2007-05
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/11336/103134
Bidon Chanal, Axel; Marti, Marcelo Adrian; Estrin, Dario Ariel; Luque, Javier F. ; Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis; American Chemical Society; Journal of the American Chemical Society; 129; 21; 5-2007; 6782-6788
0002-7863
CONICET Digital
CONICET
url http://hdl.handle.net/11336/103134
identifier_str_mv Bidon Chanal, Axel; Marti, Marcelo Adrian; Estrin, Dario Ariel; Luque, Javier F. ; Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis; American Chemical Society; Journal of the American Chemical Society; 129; 21; 5-2007; 6782-6788
0002-7863
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1021/ja0689987
info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/ja0689987
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
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
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
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
_version_ 1799195671479189504
spelling Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosisBidon Chanal, AxelMarti, Marcelo AdrianEstrin, Dario ArielLuque, Javier F.truncated hemoglobinmolecular dynamicshttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Truncated hemoglobin-N is believed to constitute a defense mechanism of Mycobacterium tuberculosis against NO produced by macrophages, which is converted to the harmless nitrate anion. This process is catalyzed very efficiently, as the enzyme activity is limited by ligand diffusion. By using extended molecular dynamics simulations we explore the mechanism that regulates ligand diffusion and, particularly, the role played by residues that assist binding of O2 to the heme group. Our data strongly support the hypothesis that the access of NO to the heme cavity is dynamically regulated by the TyrB10-GlnE11 pair, which acts as a molecular switch that controls opening of the ligand diffusion tunnel. Binding of O2 to the heme group triggers local conformational changes in the TyrB10-GlnE11 pair, which favor opening of the PheE15 gate residue through global changes in the essential motions of the protein skeleton. The complex pattern of conformational changes triggered upon O2 binding is drastically altered in the GlnE11fAla and TyrB10fPhe mutants, which justifies the poor enzymatic activity observed experimentally for the TyrB10fPhe form. The results support a molecular mechanism evolved to ensure access of NO to the heme cavity in the oxygenated form of the protein, which should warrant survival of the microorganism under stress conditions.Fil: Bidon Chanal, Axel. Universidad de Barcelona; EspañaFil: Marti, Marcelo Adrian. 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. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; 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; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Inorgánica, Analítica y Química Física; ArgentinaFil: Luque, Javier F.. Universidad de Barcelona; EspañaAmerican Chemical Society2007-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/103134Bidon Chanal, Axel; Marti, Marcelo Adrian; Estrin, Dario Ariel; Luque, Javier F. ; Dynamical Regulation of Ligand Migration by a Gate-Opening Molecular Switch in Truncated Hemoglobin-N from Mycobacterium tuberculosis; American Chemical Society; Journal of the American Chemical Society; 129; 21; 5-2007; 6782-67880002-7863CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1021/ja0689987info:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/ja0689987info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2024-05-08T13:59:50Zoai:ri.conicet.gov.ar:11336/103134instacron: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:34982024-05-08 13:59:50.402CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
score 15,811543

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