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

AUTOR(ES)

Milani, Mario

FONTE

Oxford University Press

RESUMO

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 stereochemistry and the protein matrix tunnel may promote O2/NO chemistry in vivo, as a M.tuberculosis defense mechanism against macrophage nitrosative stress.

Documentos Relacionados

• Ozone Model for Bonding of an O2 to Heme in Oxyhemoglobin
• Geminate recombination of O2 and hemoglobin.
• Hemoglobin conformation couples erythrocyte S-nitrosothiol content to O2 gradients
• Nature of O2 and CO binding to metalloporphyrins and heme proteins.
• Drought Stress, Permeability to O2 Diffusion, and the Respiratory Kinetics of Soybean Root Nodules.