Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O
Mycobacterium tuberculosis is the causative agent of human tuberculosis, one of the most prevalent infectious diseases in the world. Its genome hosts the glbN and glbO genes coding for two proteins, truncated hemoglobin N (trHbN) and truncated hemoglobin O (trHbO), that belong to different groups (I...
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2008
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paper:paper_08873585_v73_n2_p372_Boechi2023-06-08T15:46:47Z Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel Jarzynski Ligand migration Molecular dynamics Mycobacterium tuberculosis Truncated hemoglobin hemoprotein nitric oxide synthase truncated hemoglobin o unclassified drug article computer simulation molecular dynamics Mycobacterium tuberculosis nonhuman oxygen affinity priority journal protein expression protein function protein structure Bacterial Proteins Crystallography, X-Ray Ligands Mutant Proteins Mycobacterium tuberculosis Thermodynamics Truncated Hemoglobins Mycobacterium tuberculosis Mycobacterium tuberculosis is the causative agent of human tuberculosis, one of the most prevalent infectious diseases in the world. Its genome hosts the glbN and glbO genes coding for two proteins, truncated hemoglobin N (trHbN) and truncated hemoglobin O (trHbO), that belong to different groups (I and II, respectively) of the recently discovered trHb family of hemeproteins. The different expression pattern and kinetics rates constants for ligand association and NO oxidation rate suggest different functions for these proteins. Previous experimental and theoretical studies showed that, in trHbs, ligand migration along the internal tunnel cavity system is a key issue in determining the ligand-binding characteristics. The X-ray structure of trHbO has been solved and shows several internal cavities and secondary-docking sites. In this work, we present an extensive investigation of the tunnel/cavity system of M. tuberculosis trHbO by means of computer-simulation techniques. We have computed the free-energy profiles for ligand migration along three found tunnels in the oxy and deoxy w.t. and mutant trHbO proteins. Our results show that multiple-ligand migration paths are possible and that several conserved residues such as TrpG8 play a key role in the ligand-migration regulation. © 2008 Wiley-Liss, Inc. Fil:Boechi, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Martí, M.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. 2008 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v73_n2_p372_Boechi http://hdl.handle.net/20.500.12110/paper_08873585_v73_n2_p372_Boechi |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Jarzynski Ligand migration Molecular dynamics Mycobacterium tuberculosis Truncated hemoglobin hemoprotein nitric oxide synthase truncated hemoglobin o unclassified drug article computer simulation molecular dynamics Mycobacterium tuberculosis nonhuman oxygen affinity priority journal protein expression protein function protein structure Bacterial Proteins Crystallography, X-Ray Ligands Mutant Proteins Mycobacterium tuberculosis Thermodynamics Truncated Hemoglobins Mycobacterium tuberculosis |
| spellingShingle |
Jarzynski Ligand migration Molecular dynamics Mycobacterium tuberculosis Truncated hemoglobin hemoprotein nitric oxide synthase truncated hemoglobin o unclassified drug article computer simulation molecular dynamics Mycobacterium tuberculosis nonhuman oxygen affinity priority journal protein expression protein function protein structure Bacterial Proteins Crystallography, X-Ray Ligands Mutant Proteins Mycobacterium tuberculosis Thermodynamics Truncated Hemoglobins Mycobacterium tuberculosis Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| topic_facet |
Jarzynski Ligand migration Molecular dynamics Mycobacterium tuberculosis Truncated hemoglobin hemoprotein nitric oxide synthase truncated hemoglobin o unclassified drug article computer simulation molecular dynamics Mycobacterium tuberculosis nonhuman oxygen affinity priority journal protein expression protein function protein structure Bacterial Proteins Crystallography, X-Ray Ligands Mutant Proteins Mycobacterium tuberculosis Thermodynamics Truncated Hemoglobins Mycobacterium tuberculosis |
| description |
Mycobacterium tuberculosis is the causative agent of human tuberculosis, one of the most prevalent infectious diseases in the world. Its genome hosts the glbN and glbO genes coding for two proteins, truncated hemoglobin N (trHbN) and truncated hemoglobin O (trHbO), that belong to different groups (I and II, respectively) of the recently discovered trHb family of hemeproteins. The different expression pattern and kinetics rates constants for ligand association and NO oxidation rate suggest different functions for these proteins. Previous experimental and theoretical studies showed that, in trHbs, ligand migration along the internal tunnel cavity system is a key issue in determining the ligand-binding characteristics. The X-ray structure of trHbO has been solved and shows several internal cavities and secondary-docking sites. In this work, we present an extensive investigation of the tunnel/cavity system of M. tuberculosis trHbO by means of computer-simulation techniques. We have computed the free-energy profiles for ligand migration along three found tunnels in the oxy and deoxy w.t. and mutant trHbO proteins. Our results show that multiple-ligand migration paths are possible and that several conserved residues such as TrpG8 play a key role in the ligand-migration regulation. © 2008 Wiley-Liss, Inc. |
| author |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_facet |
Boechi, Leonardo Martí, Marcelo Adrián Estrin, Dario Ariel |
| author_sort |
Boechi, Leonardo |
| title |
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| title_short |
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| title_full |
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| title_fullStr |
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| title_full_unstemmed |
Structural determinants of ligand migration in Mycobacterium tuberculosis truncated hemoglobin O |
| title_sort |
structural determinants of ligand migration in mycobacterium tuberculosis truncated hemoglobin o |
| publishDate |
2008 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08873585_v73_n2_p372_Boechi http://hdl.handle.net/20.500.12110/paper_08873585_v73_n2_p372_Boechi |
| work_keys_str_mv |
AT boechileonardo structuraldeterminantsofligandmigrationinmycobacteriumtuberculosistruncatedhemoglobino AT martimarceloadrian structuraldeterminantsofligandmigrationinmycobacteriumtuberculosistruncatedhemoglobino AT estrindarioariel structuraldeterminantsofligandmigrationinmycobacteriumtuberculosistruncatedhemoglobino |
| _version_ |
1768544231379435520 |