title: Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N.
abstract: The capability of Mycobacterium tuberculosis to rest in latency in the infected organism appears to be related to the disposal of detoxification mechanisms, which converts the nitric oxide (NO) produced by macrophages during the initial growth infection stage into a nitrate anion. Such a reaction appears to be associated with the truncated hemoglobin N (trHbN). Even though previous experimental and theoretical studies have examined the pathways used by NO and O2 to access the heme cavity, the eggression pathway of the nitrate anion is still a challenging question. In this work we present results obtained by means of classical and quantum chemistry simulations that show that trHbN is able to release rapidly the nitrate anion using an eggression pathway other than those used for the entry of both O2 and NO and that its release is promoted by hydration of the heme cavity. These results provide a detailed understanding of the molecular basis of the NO detoxification mechanism used by trHbN to guarantee an efficient NO detoxification and thus warrant survival of the microorganism under stress conditions.
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón 2, Buenos Aires, C1428EHA, Argentina.
authors.forename: Marcelo A
authors.initials: MA
authors.lastname: Martí
authors.forename: Axel
authors.initials: A
authors.lastname: Bidon-Chanal
authors.forename: Alejandro
authors.initials: A
authors.lastname: Crespo
authors.forename: Syun-Ru
authors.initials: SR
authors.lastname: Yeh
authors.forename: Victor
authors.initials: V
authors.lastname: Guallar
authors.forename: F Javier
authors.initials: FJ
authors.lastname: Luque
authors.forename: Darío A
authors.initials: DA
authors.lastname: Estrin
mesh_terms: D000838:Anions / Q000737:chemistry; D001665:Binding Sites; D003198:Computer Simulation; D006455:Hemoglobins, Abnormal / Q000737:chemistry* / Q000378:metabolism*; D008024:Ligands; D008958:Models, Molecular; D009169:Mycobacterium tuberculosis / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D009566:Nitrates / Q000737:chemistry / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism* / Q000633:toxicity*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D000838:Anions; D006455:Hemoglobins, Abnormal; D008024:Ligands; D009566:Nitrates; D014867:Water; D009569:Nitric Oxide; C031031:hemoglobins N