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Truncated hemoglobins and nitric oxide action
Mario Milani1, Alessandra Pesce, Hugues Ouellet
1Istituto Giannina Gaslini, Largo Girolamo Gaslini, 5. 16147 Genova, Italy.
IUBMB Life
|January 9, 2004
Summary
Truncated hemoglobins (trHbs) are a distinct protein group. Mycobacterium tuberculosis trHbN efficiently converts nitric oxide to nitrate, potentially protecting against host immune responses.
Area of Science:
- Biochemistry
- Structural Biology
- Microbiology
Background:
- Truncated hemoglobins (trHbs) represent a distinct subfamily within the hemoglobin superfamily, characterized by shorter amino acid sequences (115-130 residues) and limited sequence similarity to other hemoglobins.
- trHbs possess a unique tertiary structure featuring a 2-on-2 alpha-helical sandwich that encases a hydrophobic cavity/tunnel system.
- This internal tunnel system may facilitate ligand diffusion to the heme active site.
Purpose of the Study:
- To investigate the structural and functional characteristics of truncated hemoglobins, specifically focusing on Mycobacterium tuberculosis trHbN.
- To elucidate the role of the unique structural features of trHbN, including its hydrophobic tunnel and heme distal site, in ligand interactions and enzymatic activity.
- To explore the potential physiological significance of trHbN's nitric oxide dioxygenation activity in the context of host-pathogen interactions.
Main Methods:
- Structural analysis of truncated hemoglobins, highlighting the 2-on-2 alpha-helical sandwich and internal hydrophobic cavity/tunnel system.
- In vitro experiments to assess the enzymatic activity of Mycobacterium tuberculosis trHbN, particularly its interaction with nitric oxide.
- Characterization of the heme distal site, including the hydrogen bond network involving TyrB10 and GlnE11, and its role in ligand binding.
Main Results:
- Mycobacterium tuberculosis trHbN demonstrates efficient dioxygenation of nitric oxide (NO) to nitrate (NO3-).
- The heme-bound oxygen in trHbN is integrated into an extended hydrogen bond network at the heme distal site, involving TyrB10 and GlnE11.
- The study proposes that the overall architecture of trHbN, including its tunnel system and hydrogen-bonded network, is optimized for the conversion of NO to nitrate.
Conclusions:
- Mycobacterium tuberculosis trHbN possesses a unique structure that facilitates the conversion of reactive nitric oxide to harmless nitrate.
- This enzymatic activity may serve as a defense mechanism for M. tuberculosis against nitrosative stress imposed by host macrophages during infection.
- The findings suggest a pseudo-catalytic role for trHbN, highlighting the functional significance of its specialized protein architecture.