Mechanism of Product Release in NO Detoxification from Mycobacterium tuberculosis Truncated Hemoglobin N

M. A. MARTI; A. BIDON CHANAL; A. CRESPO; S. YEH; V. GUALLAR; F.J. LUQUE; D.A. ESTRIN

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

American Chemical Society

Año: 2008 vol. 130 p. 1688 - 1696

0002-7863

            The capability of Mycobacterium tuberculosis to rest in latency in the infected organism appearsto be related to the disposal of detoxification mechanisms, which converts the nitric oxide (NO) producedby macrophages during the initial growth infection stage into a nitrate anion. Such a reaction appears to beassociated with the truncated hemoglobin N (trHbN). Even though previous experimental and theoreticalstudies have examined the pathways used by NO and O2 to access the heme cavity, the eggression pathwayof the nitrate anion is still a challenging question. In this work we present results obtained by means ofclassical and quantum chemistry simulations that show that trHbN is able to release rapidly the nitrateanion using an eggression pathway other than those used for the entry of both O2 and NO and that itsrelease is promoted by hydration of the heme cavity. These results provide a detailed understanding of themolecular basis of the NO detoxification mechanism used by trHbN to guarantee an efficient NOdetoxification and thus warrant survival of the microorganism under stress conditions.