Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis
- Autores
- Lama, Amriti; Pawarta, Sudesh; Bidon Chanal, Axel; Anand, Arvind; Gelpi, José Luis; Arya, Swati; Marti, Marcelo Adrian; Estrin, Dario Ariel; Luque, F. Javier; Dikshit, Kanak
- Año de publicación
- 2009
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress. The protein carries a tunnel system composed of a short and a long tunnel branch that has been proposed to facilitate diatomic ligand migration to the heme and an unusual Pre-A motif at the N terminus, which does not contribute significantly to the structural integrity of the protein, as it protrudes out of the compact globin fold. Strikingly, deletion of Pre-A region from the M. tuberculosis HbN drastically reduces its ability to scavenge nitric oxide (NO), whereas its insertion at the N terminus of Pre-A lacking HbN of Mycobacterium smegmatis improved its nitric-oxide dioxygenase activity. Titration of the oxygenated adduct of HbN and its mutants with NO indicated that the stoichiometric oxidation of protein is severalfold slower when the Pre-A region is deleted in HbN. Molecular dynamics simulations show that the excision of Pre-A motif results in distinct changes in the protein dynamics, which cause the gate of the tunnel long branch to be trapped into a closed conformation, thus impeding migration of diatomic ligands toward the heme active site. The present study, thus, unequivocally demonstrates vital function of Pre-A region in NO scavenging and unravels its unique role by which HbN might attain its efficient NO-detoxification ability.
Fil: Lama, Amriti. Council of Scientific and Industrial Research; India
Fil: Pawarta, Sudesh. Council of Scientific and Industrial Research; India
Fil: Bidon Chanal, Axel. Universitat de Barcelona; España
Fil: Anand, Arvind. Council of Scientific and Industrial Research; India
Fil: Gelpi, José Luis. Universitat de Barcelona; España
Fil: Arya, Swati. Council of Scientific and Industrial Research; India
Fil: 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
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: Luque, F. Javier. Universitat de Barcelona; España
Fil: Dikshit, Kanak. Council of Scientific and Industrial Research; India - Materia
-
truncated hemoglobin
molecular dynamics - 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:11336/75572
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Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium TuberculosisLama, AmritiPawarta, SudeshBidon Chanal, AxelAnand, ArvindGelpi, José LuisArya, SwatiMarti, Marcelo AdrianEstrin, Dario ArielLuque, F. JavierDikshit, Kanaktruncated hemoglobinmolecular dynamicshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress. The protein carries a tunnel system composed of a short and a long tunnel branch that has been proposed to facilitate diatomic ligand migration to the heme and an unusual Pre-A motif at the N terminus, which does not contribute significantly to the structural integrity of the protein, as it protrudes out of the compact globin fold. Strikingly, deletion of Pre-A region from the M. tuberculosis HbN drastically reduces its ability to scavenge nitric oxide (NO), whereas its insertion at the N terminus of Pre-A lacking HbN of Mycobacterium smegmatis improved its nitric-oxide dioxygenase activity. Titration of the oxygenated adduct of HbN and its mutants with NO indicated that the stoichiometric oxidation of protein is severalfold slower when the Pre-A region is deleted in HbN. Molecular dynamics simulations show that the excision of Pre-A motif results in distinct changes in the protein dynamics, which cause the gate of the tunnel long branch to be trapped into a closed conformation, thus impeding migration of diatomic ligands toward the heme active site. The present study, thus, unequivocally demonstrates vital function of Pre-A region in NO scavenging and unravels its unique role by which HbN might attain its efficient NO-detoxification ability.Fil: Lama, Amriti. Council of Scientific and Industrial Research; IndiaFil: Pawarta, Sudesh. Council of Scientific and Industrial Research; IndiaFil: Bidon Chanal, Axel. Universitat de Barcelona; EspañaFil: Anand, Arvind. Council of Scientific and Industrial Research; IndiaFil: Gelpi, José Luis. Universitat de Barcelona; EspañaFil: Arya, Swati. Council of Scientific and Industrial Research; IndiaFil: 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; 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: Luque, F. Javier. Universitat de Barcelona; EspañaFil: Dikshit, Kanak. Council of Scientific and Industrial Research; IndiaAmerican Society for Biochemistry and Molecular Biology2009info: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/11336/75572Lama, Amriti; Pawarta, Sudesh; Bidon Chanal, Axel; Anand, Arvind; Gelpi, José Luis; et al.; Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 284; 2009; 14457-144680021-9258CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.jbc.org/content/284/21/14457.longinfo:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M807436200info:eu-repo/semantics/altIdentifier/pmid/19329431info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:54:37Zoai:ri.conicet.gov.ar:11336/75572instacron: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 09:54:37.284CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
title |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
spellingShingle |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis Lama, Amriti truncated hemoglobin molecular dynamics |
title_short |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
title_full |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
title_fullStr |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
title_full_unstemmed |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
title_sort |
Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis |
dc.creator.none.fl_str_mv |
Lama, Amriti Pawarta, Sudesh Bidon Chanal, Axel Anand, Arvind Gelpi, José Luis Arya, Swati Marti, Marcelo Adrian Estrin, Dario Ariel Luque, F. Javier Dikshit, Kanak |
author |
Lama, Amriti |
author_facet |
Lama, Amriti Pawarta, Sudesh Bidon Chanal, Axel Anand, Arvind Gelpi, José Luis Arya, Swati Marti, Marcelo Adrian Estrin, Dario Ariel Luque, F. Javier Dikshit, Kanak |
author_role |
author |
author2 |
Pawarta, Sudesh Bidon Chanal, Axel Anand, Arvind Gelpi, José Luis Arya, Swati Marti, Marcelo Adrian Estrin, Dario Ariel Luque, F. Javier Dikshit, Kanak |
author2_role |
author author author author author author author author author |
dc.subject.none.fl_str_mv |
truncated hemoglobin molecular dynamics |
topic |
truncated hemoglobin molecular dynamics |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress. The protein carries a tunnel system composed of a short and a long tunnel branch that has been proposed to facilitate diatomic ligand migration to the heme and an unusual Pre-A motif at the N terminus, which does not contribute significantly to the structural integrity of the protein, as it protrudes out of the compact globin fold. Strikingly, deletion of Pre-A region from the M. tuberculosis HbN drastically reduces its ability to scavenge nitric oxide (NO), whereas its insertion at the N terminus of Pre-A lacking HbN of Mycobacterium smegmatis improved its nitric-oxide dioxygenase activity. Titration of the oxygenated adduct of HbN and its mutants with NO indicated that the stoichiometric oxidation of protein is severalfold slower when the Pre-A region is deleted in HbN. Molecular dynamics simulations show that the excision of Pre-A motif results in distinct changes in the protein dynamics, which cause the gate of the tunnel long branch to be trapped into a closed conformation, thus impeding migration of diatomic ligands toward the heme active site. The present study, thus, unequivocally demonstrates vital function of Pre-A region in NO scavenging and unravels its unique role by which HbN might attain its efficient NO-detoxification ability. Fil: Lama, Amriti. Council of Scientific and Industrial Research; India Fil: Pawarta, Sudesh. Council of Scientific and Industrial Research; India Fil: Bidon Chanal, Axel. Universitat de Barcelona; España Fil: Anand, Arvind. Council of Scientific and Industrial Research; India Fil: Gelpi, José Luis. Universitat de Barcelona; España Fil: Arya, Swati. Council of Scientific and Industrial Research; India Fil: 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 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: Luque, F. Javier. Universitat de Barcelona; España Fil: Dikshit, Kanak. Council of Scientific and Industrial Research; India |
description |
Mycobacterium tuberculosis truncated hemoglobin, HbN, is endowed with a potent nitric-oxide dioxygenase activity and has been found to relieve nitrosative stress and enhance in vivo survival of a heterologous host, Salmonella enterica Typhimurium, within the macrophages. These findings implicate involvement of HbN in the defense of M. tuberculosis against nitrosative stress. The protein carries a tunnel system composed of a short and a long tunnel branch that has been proposed to facilitate diatomic ligand migration to the heme and an unusual Pre-A motif at the N terminus, which does not contribute significantly to the structural integrity of the protein, as it protrudes out of the compact globin fold. Strikingly, deletion of Pre-A region from the M. tuberculosis HbN drastically reduces its ability to scavenge nitric oxide (NO), whereas its insertion at the N terminus of Pre-A lacking HbN of Mycobacterium smegmatis improved its nitric-oxide dioxygenase activity. Titration of the oxygenated adduct of HbN and its mutants with NO indicated that the stoichiometric oxidation of protein is severalfold slower when the Pre-A region is deleted in HbN. Molecular dynamics simulations show that the excision of Pre-A motif results in distinct changes in the protein dynamics, which cause the gate of the tunnel long branch to be trapped into a closed conformation, thus impeding migration of diatomic ligands toward the heme active site. The present study, thus, unequivocally demonstrates vital function of Pre-A region in NO scavenging and unravels its unique role by which HbN might attain its efficient NO-detoxification ability. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009 |
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/11336/75572 Lama, Amriti; Pawarta, Sudesh; Bidon Chanal, Axel; Anand, Arvind; Gelpi, José Luis; et al.; Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 284; 2009; 14457-14468 0021-9258 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/75572 |
identifier_str_mv |
Lama, Amriti; Pawarta, Sudesh; Bidon Chanal, Axel; Anand, Arvind; Gelpi, José Luis; et al.; Role of the pre-A motif in nitric oxide scavenging by truncated hemoglobin HbN of Mycobacterium Tuberculosis; American Society for Biochemistry and Molecular Biology; Journal of Biological Chemistry (online); 284; 2009; 14457-14468 0021-9258 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://www.jbc.org/content/284/21/14457.long info:eu-repo/semantics/altIdentifier/doi/10.1074/jbc.M807436200 info:eu-repo/semantics/altIdentifier/pmid/19329431 |
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 Society for Biochemistry and Molecular Biology |
publisher.none.fl_str_mv |
American Society for Biochemistry and Molecular Biology |
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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1844613657787367424 |
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13.070432 |