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 journalArticle

27 Citations (Scopus)

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

Fingerprint

Truncated Hemoglobins
Detoxification
Hemoglobin
Nitric oxide
Mycobacterium tuberculosis
Nitric Oxide
Nitrates
Anions
Negative ions
Heme
Quantum chemistry
Macrophages
Hydration
Microorganisms
Theoretical Models
hemoglobins N
Growth
Infection

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N. / Martí, Marcelo A.; Bidon-Chanal, Axel; Crespo, Alejandro; Yeh, Syun-Ru; Guallar, Victor; Luque, F. Javier; Estrin, Darío A.

In: Journal of the American Chemical Society, Vol. 130, No. 5, 06.02.2008, p. 1688-1693.

Research output: Contribution to journalArticle

Martí, Marcelo A. ; Bidon-Chanal, Axel ; Crespo, Alejandro ; Yeh, Syun-Ru ; Guallar, Victor ; Luque, F. Javier ; Estrin, Darío A. / Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N. In: Journal of the American Chemical Society. 2008 ; Vol. 130, No. 5. pp. 1688-1693.
@article{911010c0b0ff481dab10740896c0f408,
title = "Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N",
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.",
author = "Mart{\'i}, {Marcelo A.} and Axel Bidon-Chanal and Alejandro Crespo and Syun-Ru Yeh and Victor Guallar and Luque, {F. Javier} and Estrin, {Dar{\'i}o A.}",
year = "2008",
month = "2",
day = "6",
doi = "10.1021/ja076853+",
language = "English (US)",
volume = "130",
pages = "1688--1693",
journal = "Journal of the American Chemical Society",
issn = "0002-7863",
publisher = "American Chemical Society",
number = "5",

}

TY - JOUR

T1 - Mechanism of product release in NO detoxification from Mycobacterium tuberculosis truncated hemoglobin N

AU - Martí, Marcelo A.

AU - Bidon-Chanal, Axel

AU - Crespo, Alejandro

AU - Yeh, Syun-Ru

AU - Guallar, Victor

AU - Luque, F. Javier

AU - Estrin, Darío A.

PY - 2008/2/6

Y1 - 2008/2/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=38949211777&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=38949211777&partnerID=8YFLogxK

U2 - 10.1021/ja076853+

DO - 10.1021/ja076853+

M3 - Article

C2 - 18189394

AN - SCOPUS:38949211777

VL - 130

SP - 1688

EP - 1693

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

SN - 0002-7863

IS - 5

ER -