Artículo

Boechi, L.; Boron, I.; Bustamante, J.P.; Davidge, K.S.; Singh, S.; Bowman, L.A.H.; Tinajero-Trejo, M.; Carballal, S.; Radi, R.; Poole, R.K.; Dikshit, K.; Estrin, D.A.; Marti, M.A. "Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules" (2015) F1000Research. 4
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Abstract:

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 O 2 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. © 2015.

Registro:

Documento: Artículo
Título:Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules
Autor:Boechi, L.; Boron, I.; Bustamante, J.P.; Davidge, K.S.; Singh, S.; Bowman, L.A.H.; Tinajero-Trejo, M.; Carballal, S.; Radi, R.; Poole, R.K.; Dikshit, K.; Estrin, D.A.; Marti, M.A.
Filiación:Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Departamento de Química Inorgánica, Analítica y Química Física, INQUIMAE-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Centre for Biomolecular Sciences, The University of Nottingham, Nottingham, NG7 2RD, United Kingdom
Institute of Microbial Technology, CSIR, Chandigarh, 160036, India
Sir William Dunn School of Pathology, University of Oxford, Oxford, OX1 3RE, United Kingdom
Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, S10 2TN, United Kingdom
Departamento de Bioquímica and Center for Free Radical and Biomedical Research, Facultad de Medicina, Universidad de la República, Montevideo, 11100, Uruguay
Instituto de Cálculo, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428EGA, Argentina
Palabras clave:carbon monoxide; nitric oxide; truncated hemoglobin; active site water molecule; Article; bacterial kinetics; computer model; controlled study; decomposition; internal tunnel; molecular dynamics; molecule; mutant; mutation; Mycobacterium tuberculosis; protein structure; wild type
Año:2015
Volumen:4
DOI: http://dx.doi.org/10.12688/f1000research.5921.2
Título revista:F1000Research
Título revista abreviado:F1000 Res.
ISSN:20461402
CAS:carbon monoxide, 630-08-0; nitric oxide, 10102-43-9
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_20461402_v4_n_p_Boechi

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Citas:

---------- APA ----------
Boechi, L., Boron, I., Bustamante, J.P., Davidge, K.S., Singh, S., Bowman, L.A.H., Tinajero-Trejo, M.,..., Marti, M.A. (2015) . Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules. F1000Research, 4.
http://dx.doi.org/10.12688/f1000research.5921.2
---------- CHICAGO ----------
Boechi, L., Boron, I., Bustamante, J.P., Davidge, K.S., Singh, S., Bowman, L.A.H., et al. "Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules" . F1000Research 4 (2015).
http://dx.doi.org/10.12688/f1000research.5921.2
---------- MLA ----------
Boechi, L., Boron, I., Bustamante, J.P., Davidge, K.S., Singh, S., Bowman, L.A.H., et al. "Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules" . F1000Research, vol. 4, 2015.
http://dx.doi.org/10.12688/f1000research.5921.2
---------- VANCOUVER ----------
Boechi, L., Boron, I., Bustamante, J.P., Davidge, K.S., Singh, S., Bowman, L.A.H., et al. Ligand uptake in Mycobacterium tuberculosis truncated hemoglobins is controlled by both internal tunnels and active site water molecules. F1000 Res. 2015;4.
http://dx.doi.org/10.12688/f1000research.5921.2