Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N

Mycobacterium tuberculosis, the causative agent of human tuberculosis, is forced into latency by nitric oxide produced by macrophages during infection. In response to nitrosative stress M. tuberculosis has evolved a defense mechanism that relies on the oxygenated form of "truncated hemoglobin&q...

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Autores principales:	Bidon-Chanal, A., Martí, M.A., Crespo, A., Milani, M., Orozco, M., Bolognesi, M., Luque, F.J., Estrin, D.A.
Formato:	JOUR
Materias:	Ligand migration M. tuberculosis Molecular dynamics Nitric oxide deoxy truncated hemoglobin n dioxygenase heme hemoglobin ligand nitrate nitric oxide oxygen truncated hemoglobin n unclassified drug article bioinformatics conformational transition crystal structure defense mechanism diffusion latent period macrophage molecular dynamics Mycobacterium tuberculosis nitrosation nonhuman oxygen affinity priority journal protein conformation protein function simulation structure analysis X ray crystallography
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_08873585_v64_n2_p457_BidonChanal
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	todo:paper_08873585_v64_n2_p457_BidonChanal
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spelling	todo:paper_08873585_v64_n2_p457_BidonChanal2023-10-03T15:40:50Z Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N Bidon-Chanal, A. Martí, M.A. Crespo, A. Milani, M. Orozco, M. Bolognesi, M. Luque, F.J. Estrin, D.A. Ligand migration M. tuberculosis Molecular dynamics Nitric oxide deoxy truncated hemoglobin n dioxygenase heme hemoglobin ligand nitrate nitric oxide oxygen truncated hemoglobin n unclassified drug article bioinformatics conformational transition crystal structure defense mechanism diffusion latent period macrophage molecular dynamics Mycobacterium tuberculosis nitrosation nonhuman oxygen affinity priority journal protein conformation protein function simulation structure analysis X ray crystallography Mycobacterium tuberculosis Mycobacterium tuberculosis, the causative agent of human tuberculosis, is forced into latency by nitric oxide produced by macrophages during infection. In response to nitrosative stress M. tuberculosis has evolved a defense mechanism that relies on the oxygenated form of "truncated hemoglobin" N (trHbN), formally acting as NO-dioxygenase, yielding the harmless nitrate ion. X-ray crystal structures have shown that trHbN hosts a two-branched protein matrix tunnel system, proposed to control diatomic ligand migration to the heme, as the rate-limiting step in NO conversion to nitrate. Extended molecular dynamics simulations (0.1 μs), employed here to characterize the factors controlling diatomic ligand diffusion through the apolar tunnel system, suggest that O2 migration in deoxy-trHbN is restricted to a short branch of the tunnel, and that O2 binding to the heme drives conformational and dynamical fluctuations promoting NO migration through the long tunnel branch. The simulation results suggest that trHbN has evolved a dual-path mechanism for migration of O2 and NO to the heme, to achieve the most efficient NO detoxification. © 2006 Wiley-Liss, Inc. Fil:Martí, M.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Crespo, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Estrin, D.A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_08873585_v64_n2_p457_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 M. tuberculosis Molecular dynamics Nitric oxide deoxy truncated hemoglobin n dioxygenase heme hemoglobin ligand nitrate nitric oxide oxygen truncated hemoglobin n unclassified drug article bioinformatics conformational transition crystal structure defense mechanism diffusion latent period macrophage molecular dynamics Mycobacterium tuberculosis nitrosation nonhuman oxygen affinity priority journal protein conformation protein function simulation structure analysis X ray crystallography Mycobacterium tuberculosis
spellingShingle	Ligand migration M. tuberculosis Molecular dynamics Nitric oxide deoxy truncated hemoglobin n dioxygenase heme hemoglobin ligand nitrate nitric oxide oxygen truncated hemoglobin n unclassified drug article bioinformatics conformational transition crystal structure defense mechanism diffusion latent period macrophage molecular dynamics Mycobacterium tuberculosis nitrosation nonhuman oxygen affinity priority journal protein conformation protein function simulation structure analysis X ray crystallography Mycobacterium tuberculosis Bidon-Chanal, A. Martí, M.A. Crespo, A. Milani, M. Orozco, M. Bolognesi, M. Luque, F.J. Estrin, D.A. Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
topic_facet	Ligand migration M. tuberculosis Molecular dynamics Nitric oxide deoxy truncated hemoglobin n dioxygenase heme hemoglobin ligand nitrate nitric oxide oxygen truncated hemoglobin n unclassified drug article bioinformatics conformational transition crystal structure defense mechanism diffusion latent period macrophage molecular dynamics Mycobacterium tuberculosis nitrosation nonhuman oxygen affinity priority journal protein conformation protein function simulation structure analysis X ray crystallography Mycobacterium tuberculosis
description	Mycobacterium tuberculosis, the causative agent of human tuberculosis, is forced into latency by nitric oxide produced by macrophages during infection. In response to nitrosative stress M. tuberculosis has evolved a defense mechanism that relies on the oxygenated form of "truncated hemoglobin" N (trHbN), formally acting as NO-dioxygenase, yielding the harmless nitrate ion. X-ray crystal structures have shown that trHbN hosts a two-branched protein matrix tunnel system, proposed to control diatomic ligand migration to the heme, as the rate-limiting step in NO conversion to nitrate. Extended molecular dynamics simulations (0.1 μs), employed here to characterize the factors controlling diatomic ligand diffusion through the apolar tunnel system, suggest that O2 migration in deoxy-trHbN is restricted to a short branch of the tunnel, and that O2 binding to the heme drives conformational and dynamical fluctuations promoting NO migration through the long tunnel branch. The simulation results suggest that trHbN has evolved a dual-path mechanism for migration of O2 and NO to the heme, to achieve the most efficient NO detoxification. © 2006 Wiley-Liss, Inc.
format	JOUR
author	Bidon-Chanal, A. Martí, M.A. Crespo, A. Milani, M. Orozco, M. Bolognesi, M. Luque, F.J. Estrin, D.A.
author_facet	Bidon-Chanal, A. Martí, M.A. Crespo, A. Milani, M. Orozco, M. Bolognesi, M. Luque, F.J. Estrin, D.A.
author_sort	Bidon-Chanal, A.
title	Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
title_short	Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
title_full	Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
title_fullStr	Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
title_full_unstemmed	Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N
title_sort	ligand-induced dynamical regulation of no conversion in mycobacterium tuberculosis truncated hemoglobin-n
url	http://hdl.handle.net/20.500.12110/paper_08873585_v64_n2_p457_BidonChanal
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Ligand-induced dynamical regulation of NO conversion in Mycobacterium tuberculosis truncated hemoglobin-N

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