Product Release in NO detoxification by Mycobacterium tuberculosis Truncated Hemoglobin

MARCELO A. MARTI; AXEL BIDON-CHANAL; ALEJANDRO CRESPO; SYUN-RU YEH; FRANCISCO JAVIER LUQUE; VICTOR GUALLAR; DARIO A ESTRIN

Aarhus Denmark

Congreso; XVIIth International Conference on Dioxygen Binding and sensing Proteins; 2008

<!-- @page { size: 8.5in 11in; margin: 0.79in } P { margin-bottom: 0.08in } --> About one-third of the human population is infected by Mycobacterium tuberculosis. During the initial growth infection stage, nitric oxide (NO) produced by macrophages contributes to restrict the bacteria in latency. However, NO detoxification mechanisms have evolved in several pathogenic microorganisms. One of such mechanisms consists in the oxidation of NO with heme-bound O2 to yield the harmless nitrate ion. In M. tuberculosis such a reaction appears to be associated with the truncated hemoglobin N (trHbN). Previous experimental and theoretical studies have shown how NO, and O2 access tr Hb N active site and react efficiently yielding a trHbN-NO3 as the product. The final remaining question is then: how NO3- is released? The results presented here show that trHb N is able to release rapidly the nitrate anion using an egression pathway different for those used for the entry of both O2 and NO, and that its release is promoted by solvation of the protein active site. Our results, together with those obtained previously, allow a complete understanding of the NO detoxification process of trHb N at the molecular level.