Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N

Marcelo A. Martí, Axel Bidon-Chanal, Alejandro Crespo, Syun Ru Yeh, Victor Guallar, F. Javier Luque, Darío A. Estrin

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)1688-1693
Number of pages6
JournalJournal of the American Chemical Society
Volume130
Issue number5
DOIs
StatePublished - Feb 6 2008

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N'. Together they form a unique fingerprint.

Cite this