In Self organization of Molecular system: From Molecules and Clusters to Nanotubes and Proteins.

AXEL BIDON-CHANAL; MARCELO A MARTI; DARIO A ESTRIN; FRANCISCO JAVIER LUQUE

NATO Science for Peace and Security Series A: Chemistry and Biology.

Springer

Año: 2009; p. 33 - 47

Abstract Mycobacterium tuberculosis, the causative agent of human tuberculosis,encodes a haemoprotein named Truncated Haemoglobin N (trHbN), which in its ac-tive site transforms nitric oxide (NO) to nitrate anion .NO3 /. The NO-dioxygenaseactivity of trHbN seems to be crucial for the bacillus, which can survive underthe nitrosative stress conditions that occur upon infection of the host. As a defensemechanism against the copious amounts of NO produced by macrophages uponinfection, the protein must achieve a high level of NO-dioxygenase activity to elim-inate NO, but this is modulated by its efficiency in capturing O2 and NO. Migrationof small diatomic ligands through the protein matrix is related to the presence of adoubly branched tunnel system connecting the surface and the haem cavity site. Inthis work, we have studied the mechanism that controls ligand diffusion and productegression with state-of-the-art molecular dynamics simulations. The results supporta dual path mechanism for migration of O2 and NO through distinct branches ofthe tunnel, where migration of NO is facilitated upon binding of O2 to the haemgroup. Finally, egression of NO3 is preceded by the entrance of water to the haemcavity and occurs through a different pathway. Overall, the results highlight the inti-mate relationship between structure, dynamical behavior and biological function oftrHbN.<!-- @page { size: 8.5in 11in; margin: 0.79in } P { margin-bottom: 0.08in } -->