Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme

Mario Milani, Alessandra Pesce, Yannick Ouellet, Paolo Ascenzi, Michel Guertin, Martino Bolognesi

Research output: Contribution to journalArticle

Abstract

Macrophage-generated oxygen- and nitrogen-reactive species control the development of Mycobacterium tuberculosis infection in the host. Mycobacterium tuberculosis 'truncated hemoglobin' N (trHbN) has been related to nitric oxide (NO) detoxification, in response to macrophage nitrosative stress, during the bacterium latent infection stage. The three-dimensional structure of oxygenated trHbN, solved at 1.9 Å resolution, displays the two-over-two α-helical sandwich fold recently characterized in two homologous truncated hemoglobins, featuring an extra N-terminal α-helix and homodimeric assembly. In the absence of a polar distal E7 residue, the O2 heme ligand is stabilized by two hydrogen bonds to TyrB10(33). Strikingly, ligand diffusion to the heme in trHbN may occur via an apolar tunnel/cavity system extending for ∼28 Å through the protein matrix, connecting the heme distal cavity to two distinct protein surface sites. This unique structural feature appears to be conserved in several homologous truncated hemoglobins. It is proposed that in trHbN, heme Fe/O2 stereo-chemistry and the protein matrix tunnel may promote O2/NO chemistry in vivo, as a M.tuberculosis defense mechanism against macrophage nitrosative stress.

Original languageEnglish
Pages (from-to)3902-3909
Number of pages8
JournalEMBO Journal
Volume20
Issue number15
DOIs
Publication statusPublished - Aug 1 2001

Keywords

  • Hemoprotein structure
  • Macrophage oxidative stress
  • Mycobacterium tuberculosis
  • Nitric oxide
  • Truncated hemoglobins

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Fingerprint Dive into the research topics of 'Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme'. Together they form a unique fingerprint.

  • Cite this

    Milani, M., Pesce, A., Ouellet, Y., Ascenzi, P., Guertin, M., & Bolognesi, M. (2001). Mycobacterium tuberculosis hemoglobin N displays a protein tunnel suited for O2 diffusion to the heme. EMBO Journal, 20(15), 3902-3909. https://doi.org/10.1093/emboj/20.15.3902