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

2006 ◽  
Vol 64 (2) ◽  
pp. 457-464 ◽  
Author(s):  
Axel Bidon-Chanal ◽  
Marcelo A. Martí ◽  
Alejandro Crespo ◽  
Mario Milani ◽  
Modesto Orozco ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
No Conversion

scholarly journals Theoretical Investigations of Nitric Oxide Channeling in Mycobacterium tuberculosis Truncated Hemoglobin N

2009 ◽  
Vol 97 (11) ◽  
pp. 2967-2977 ◽  
Author(s):  
Richard Daigle ◽  
Julie-Anne Rousseau ◽  
Michel Guertin ◽  
Patrick Lagüe
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
Theoretical Investigations

scholarly journals Role of PheE15 Gate in Ligand Entry and Nitric Oxide Detoxification Function of Mycobacterium tuberculosis Truncated Hemoglobin N

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49291 ◽  
Author(s):  
Ana Oliveira ◽  
Sandeep Singh ◽  
Axel Bidon-Chanal ◽  
Flavio Forti ◽  
Marcelo A. Martí ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
Nitric Oxide Detoxification

scholarly journals Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 22 ◽  
Author(s):  
Ignacio Boron ◽  
Juan Pablo Bustamante ◽  
Kelly S Davidge ◽  
Sandip Singh ◽  
Lesley AH Bowman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Active Site ◽  
Water Molecules ◽  
Single Mutation ◽  
Truncated Hemoglobin ◽  
Kinetic Measurements ◽  
Migration Rates ◽  
Ligand Migration ◽  
Site Water ◽  
Dynamics Simulations

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels that are partially blocked by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations introduce modifications in both tunnel topologies and affect the incoming ligand capacity to displace retained water molecules at the active site. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O

2008 ◽  
Vol 73 (2) ◽  
pp. 372-379 ◽  
Author(s):  
Leonardo Boechi ◽  
Marcelo A. Martí ◽  
Mario Milani ◽  
Martino Bolognesi ◽  
F. Javier Luque ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
Structural Determinants ◽  
Ligand Migration

scholarly journals Ligand migration in the truncated hemoglobin of Mycobacterium tuberculosis

IUBMB Life ◽  
2011 ◽  
Vol 63 (3) ◽  
pp. 214-220 ◽  
Author(s):  
Maxime S. Heroux ◽  
Anne D. Mohan ◽  
Kenneth W. Olsen
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
Ligand Migration

scholarly journals Isoniazid Inhibits the Heme-Based Reactivity of Mycobacterium tuberculosis Truncated Hemoglobin N

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e69762 ◽  
Author(s):  
Paolo Ascenzi ◽  
Andrea Coletta ◽  
Yu Cao ◽  
Viviana Trezza ◽  
Loris Leboffe ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin

Ultrafast heme–ligand recombination in truncated hemoglobin HbO from Mycobacterium tuberculosis: A ligand cage

2012 ◽  
Vol 396 ◽  
pp. 10-16 ◽  
Author(s):  
Audrius Jasaitis ◽  
Hugues Ouellet ◽  
Jean-Christophe Lambry ◽  
Jean-Louis Martin ◽  
Joel M. Friedman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin

Truncated Hemoglobin O Carries an Autokinase Activity and Facilitates Adaptation of Mycobacterium tuberculosis Under Hypoxia

2020 ◽  
Vol 32 (6) ◽  
pp. 351-362
Author(s):  
Mangesh Dattu Hade ◽  
Deepti Sethi ◽  
Himani Datta ◽  
Sandeep Singh ◽  
Naveen Thakur ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Truncated Hemoglobin ◽  
Autokinase Activity

scholarly journals Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 22 ◽  
Author(s):  
Ignacio Boron ◽  
Juan Pablo Bustamante ◽  
Kelly S Davidge ◽  
Sandip Singh ◽  
Lesley AH Bowman ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Active Site ◽  
Water Molecules ◽  
Single Mutation ◽  
Truncated Hemoglobin ◽  
Kinetic Measurements ◽  
Migration Rates ◽  
Ligand Migration ◽  
Site Water ◽  
Dynamics Simulations

Mycobacterium tuberculosis, the causative agent of human tuberculosis, has two proteins belonging to the truncated hemoglobin (trHb) family. Mt-trHbN presents well-defined internal hydrophobic tunnels that allow O2 and •NO to migrate easily from the solvent to the active site, whereas Mt-trHbO possesses tunnels interrupted by a few bulky residues, particularly a tryptophan at position G8. Differential ligand migration rates allow Mt-trHbN to detoxify •NO, a crucial step for pathogen survival once under attack by the immune system, much more efficiently than Mt-trHbO. In order to investigate the differences between these proteins, we performed experimental kinetic measurements, •NO decomposition, as well as molecular dynamics simulations of the wild type Mt-trHbN and two mutants, VG8F and VG8W. These mutations affect both the tunnels accessibility as well as the affinity of distal site water molecules, thus modifying the ligand access to the iron. We found that a single mutation allows Mt-trHbN to acquire ligand migration rates comparable to those observed for Mt-trHbO, confirming that ligand migration is regulated by the internal tunnel architecture as well as by water molecules stabilized in the active site.

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