INQUIMAE   12526
INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
artículos
Título:
Structural determinants of ligand migration in M. Tuberculosis trHbO
Autor/es:
L. BOECHI; M. MARTI; M. MILANI; M. BOLOGNESI; F. J. LUQUE; D.A. ESTRIN
Revista:
PROTEINS: STRUCTURE, FUNCTION AND GENETICS
Editorial:
Wiley
Referencias:
Año: 2008 vol. 73 p. 372 - 372
ISSN:
0887-3585
Resumen:
<!-- @page { size: 21cm 29.7cm; margin: 2cm } P { margin-bottom: 0.21cm } --> 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 wt 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 rol in the ligand migration regulation.