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
.jpg) 
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/75572
Ver los metadatos del registro completo
| id | CONICETDig_dd3312ccef426d7e1a3509701068e762 | 
|---|---|
| oai_identifier_str | oai:ri.conicet.gov.ar:11336/75572 | 
| network_acronym_str | CONICETDig | 
| repository_id_str | 3498 | 
| network_name_str | CONICET Digital (CONICET) | 
| spelling | 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 Técnicas2025-10-29T11:53:50Zoai: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:34982025-10-29 11:53:50.832CONICET 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 | 
| _version_ | 1847426635917164544 | 
| score | 13.10058 |