Truncated hemoglobins and nitric oxide action.
Truncated hemoglobins (trHbs) build a separate subfamily within the hemoglobin superfamily; they are scarcely related by sequence similarity to (non-)vertebrate hemoglobins, displaying amino acid sequences in the 115-130 residue range. The trHb tertiary structure is based on a 2-on-2 alpha-helical sandwich, which hosts a unique hydrophobic cavity/tunnel system, traversing the protein matrix, from the molecular surface to the heme distal site. Such a protein matrix system may provide a path for diffusion of ligands to the heme. In Mycobacterium tuberculosis trHbN the heme-bound oxygen molecule is part of an extended hydrogen bond network including the heme distal residues TyrB10 and GlnE11. In vitro experiments have shown that M. tuberculosis trHbN supports efficiently nitric oxide dioxygenation, yielding nitrate. Such a reaction would provide a defense barrier against the nitrosative stress raised by host macrophages during lung infection. It is proposed that the whole protein architecture, the heme distal site hydrogen bonded network, and the unique protein matrix tunnel, are optimally designed to support the pseudo-catalytic role of trHbN in converting the reactive NO species into the harmless NO3-.
Milani
Mario
M
Istituto Giannina Gaslini, Largo Girolamo Gaslini, 5. 16147 Genova, Italy.
Pesce
Alessandra
A
Ouellet
Hugues
H
Guertin
Michel
M
Bolognesi
Martino
M
D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002384:Catalysis; D006418:Heme / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry* / Q000502:physiology; D008024:Ligands; D008264:Macrophages / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D009566:Nitrates / Q000737:chemistry; D009569:Nitric Oxide / Q000737:chemistry / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D054793:Truncated Hemoglobins
D001426:Bacterial Proteins; D006454:Hemoglobins; D008024:Ligands; D009566:Nitrates; D054793:Truncated Hemoglobins; D009569:Nitric Oxide; D006418:Heme; D010100:Oxygen