Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N

Mycobacterium tuberculosis, the causative agent of human tuberculosis, encodes a haemoprotein named Truncated Haemoglobin N (trHbN), which in its active site transforms nitric oxide (NO) to nitrate anion. (NO3 -). The NO-dioxygenase activity of trHbN seems to be crucial for the bacillus, which can s...

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Autores principales:	Martí, Marcelo Adrián, Estrin, Dario Ariel
Publicado:	2009
Materias:	Ligand migration Molecular simulations Mycobacterium tuberculosis NO detoxification Truncated haemoglobin N
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18746489_v_n_p33_BidonChanal http://hdl.handle.net/20.500.12110/paper_18746489_v_n_p33_BidonChanal
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_18746489_v_n_p33_BidonChanal
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spelling	paper:paper_18746489_v_n_p33_BidonChanal2023-06-08T16:30:07Z Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N Martí, Marcelo Adrián Estrin, Dario Ariel Ligand migration Molecular simulations Mycobacterium tuberculosis NO detoxification Truncated haemoglobin N Mycobacterium tuberculosis Mycobacterium tuberculosis, the causative agent of human tuberculosis, encodes a haemoprotein named Truncated Haemoglobin N (trHbN), which in its active site transforms nitric oxide (NO) to nitrate anion. (NO3 -). The NO-dioxygenase activity of trHbN seems to be crucial for the bacillus, which can survive under the nitrosative stress conditions that occur upon infection of the host. As a defense mechanism against the copious amounts of NO produced by macrophages upon infection, the protein must achieve a high level of NO-dioxygenase activity to eliminate NO, but this is modulated by its efficiency in capturing O2 and NO. Migration of small diatomic ligands through the protein matrix is related to the presence of a doubly branched tunnel system connecting the surface and the haem cavity site. In this work, we have studied the mechanism that controls ligand diffusion and product egression with state-of-the-art molecular dynamics simulations. The results support a dual path mechanism for migration of O2 and NO through distinct branches of the tunnel, where migration of NO is facilitated upon binding of O2 to the haem group. Finally, egression of (NO3 -) is preceded by the entrance of water to the haem cavity and occurs through a different pathway. Overall, the results highlight the intimate relationship between structure, dynamical behavior and biological function of trHbN. © 2009 Springer Science + Business Media B.V. Fil:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrín, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2009 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18746489_v_n_p33_BidonChanal http://hdl.handle.net/20.500.12110/paper_18746489_v_n_p33_BidonChanal
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Ligand migration Molecular simulations Mycobacterium tuberculosis NO detoxification Truncated haemoglobin N Mycobacterium tuberculosis
spellingShingle	Ligand migration Molecular simulations Mycobacterium tuberculosis NO detoxification Truncated haemoglobin N Mycobacterium tuberculosis Martí, Marcelo Adrián Estrin, Dario Ariel Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
topic_facet	Ligand migration Molecular simulations Mycobacterium tuberculosis NO detoxification Truncated haemoglobin N Mycobacterium tuberculosis
description	Mycobacterium tuberculosis, the causative agent of human tuberculosis, encodes a haemoprotein named Truncated Haemoglobin N (trHbN), which in its active site transforms nitric oxide (NO) to nitrate anion. (NO3 -). The NO-dioxygenase activity of trHbN seems to be crucial for the bacillus, which can survive under the nitrosative stress conditions that occur upon infection of the host. As a defense mechanism against the copious amounts of NO produced by macrophages upon infection, the protein must achieve a high level of NO-dioxygenase activity to eliminate NO, but this is modulated by its efficiency in capturing O2 and NO. Migration of small diatomic ligands through the protein matrix is related to the presence of a doubly branched tunnel system connecting the surface and the haem cavity site. In this work, we have studied the mechanism that controls ligand diffusion and product egression with state-of-the-art molecular dynamics simulations. The results support a dual path mechanism for migration of O2 and NO through distinct branches of the tunnel, where migration of NO is facilitated upon binding of O2 to the haem group. Finally, egression of (NO3 -) is preceded by the entrance of water to the haem cavity and occurs through a different pathway. Overall, the results highlight the intimate relationship between structure, dynamical behavior and biological function of trHbN. © 2009 Springer Science + Business Media B.V.
author	Martí, Marcelo Adrián Estrin, Dario Ariel
author_facet	Martí, Marcelo Adrián Estrin, Dario Ariel
author_sort	Martí, Marcelo Adrián
title	Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
title_short	Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
title_full	Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
title_fullStr	Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
title_full_unstemmed	Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N
title_sort	exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin n
publishDate	2009
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18746489_v_n_p33_BidonChanal http://hdl.handle.net/20.500.12110/paper_18746489_v_n_p33_BidonChanal
work_keys_str_mv	AT martimarceloadrian exploringthenitricoxidedetoxificationmechanismofmycobacteriumtuberculosistruncatedhaemoglobinn AT estrindarioariel exploringthenitricoxidedetoxificationmechanismofmycobacteriumtuberculosistruncatedhaemoglobinn
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Exploring the nitric oxide detoxification mechanism of mycobacterium tuberculosis truncated haemoglobin N

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