Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N
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 ap...
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todo:paper_00027863_v130_n5_p1688_Marti2023-10-03T13:54:07Z Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N Martí, M.A. Bidon-Chanal, A. Crespo, A. Yeh, S.-R. Guallar, V. Luque, F.J. Estrin, D.A. Eggression pathway Heme cavity Mycobacterium tuberculosis Detoxification Hemoglobin Hydration Nitric oxide Quantum chemistry Bacteria heme hemoglobin hemoglobin n nitric oxide nitrite oxygen unclassified drug article bacterial growth hydration latent period macrophage molecular dynamics molecular mechanics Mycobacterium tuberculosis nonhuman quantum chemistry quantum mechanics reaction analysis simulation stress Anions Binding Sites Computer Simulation Hemoglobins, Abnormal Ligands Models, Molecular Mycobacterium tuberculosis Nitrates Nitric Oxide Protein Binding Protein Structure, Tertiary Water 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. © 2008 American Chemical Society. 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_00027863_v130_n5_p1688_Marti |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
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Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Eggression pathway Heme cavity Mycobacterium tuberculosis Detoxification Hemoglobin Hydration Nitric oxide Quantum chemistry Bacteria heme hemoglobin hemoglobin n nitric oxide nitrite oxygen unclassified drug article bacterial growth hydration latent period macrophage molecular dynamics molecular mechanics Mycobacterium tuberculosis nonhuman quantum chemistry quantum mechanics reaction analysis simulation stress Anions Binding Sites Computer Simulation Hemoglobins, Abnormal Ligands Models, Molecular Mycobacterium tuberculosis Nitrates Nitric Oxide Protein Binding Protein Structure, Tertiary Water |
| spellingShingle |
Eggression pathway Heme cavity Mycobacterium tuberculosis Detoxification Hemoglobin Hydration Nitric oxide Quantum chemistry Bacteria heme hemoglobin hemoglobin n nitric oxide nitrite oxygen unclassified drug article bacterial growth hydration latent period macrophage molecular dynamics molecular mechanics Mycobacterium tuberculosis nonhuman quantum chemistry quantum mechanics reaction analysis simulation stress Anions Binding Sites Computer Simulation Hemoglobins, Abnormal Ligands Models, Molecular Mycobacterium tuberculosis Nitrates Nitric Oxide Protein Binding Protein Structure, Tertiary Water Martí, M.A. Bidon-Chanal, A. Crespo, A. Yeh, S.-R. Guallar, V. Luque, F.J. Estrin, D.A. Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| topic_facet |
Eggression pathway Heme cavity Mycobacterium tuberculosis Detoxification Hemoglobin Hydration Nitric oxide Quantum chemistry Bacteria heme hemoglobin hemoglobin n nitric oxide nitrite oxygen unclassified drug article bacterial growth hydration latent period macrophage molecular dynamics molecular mechanics Mycobacterium tuberculosis nonhuman quantum chemistry quantum mechanics reaction analysis simulation stress Anions Binding Sites Computer Simulation Hemoglobins, Abnormal Ligands Models, Molecular Mycobacterium tuberculosis Nitrates Nitric Oxide Protein Binding Protein Structure, Tertiary Water |
| description |
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. © 2008 American Chemical Society. |
| format |
JOUR |
| author |
Martí, M.A. Bidon-Chanal, A. Crespo, A. Yeh, S.-R. Guallar, V. Luque, F.J. Estrin, D.A. |
| author_facet |
Martí, M.A. Bidon-Chanal, A. Crespo, A. Yeh, S.-R. Guallar, V. Luque, F.J. Estrin, D.A. |
| author_sort |
Martí, M.A. |
| title |
Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| title_short |
Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| title_full |
Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| title_fullStr |
Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| title_full_unstemmed |
Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N |
| title_sort |
mechanism of product release in no detoxification from mycobacterium tuberculosis truncated hemoglobin n |
| url |
http://hdl.handle.net/20.500.12110/paper_00027863_v130_n5_p1688_Marti |
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