Ultrafast heme–ligand recombination in truncated hemoglobin HbO from Mycobacterium tuberculosis: A ligand cage

• Published in: Chemical physics 2012-03, Vol.396, p.10-16
• Main Authors: Jasaitis, Audrius, Ouellet, Hugues, Lambry, Jean-Christophe, Martin, Jean-Louis, Friedman, Joel M., Guertin, Michel, Vos, Marten H.
• Format: Article
• Language: English
• Subjects: Dynamics; Heme proteins; Truncated hemoglobin; Ultrafast spectroscopy
• ISSN: 0301-0104
• DOI: 10.1016/j.chemphys.2011.04.003

In TrHbO, dissociated diatomic ligands show remarkably efficient geminate recombination that is robust against changes in close by aromatic residues. [Display omitted] ► We studied ultrafast ligand dynamics in truncated hemoglobin HbO from M. tuberculosis. ► CO, NO, and O2 all have a very low probability to escape from the heme pocket. ► Fast CO geminate rebinding is robust against changes in close aromatic residues. ► Molecular dynamics simulations suggest origins of caging. Truncated hemoglobin HbO from Mycobacterium tuberculosis displays very slow exchange of diatomic ligands with its environment. Using femtosecond spectroscopy, we show that upon photoexcitation, ligands rebind with unusual speed and efficiency. Only ∼1% O2 can escape from the heme pocket and less than 1% NO. Most remarkably, CO rebinding occurs for 95%, predominantly in 1.2ns. The general CO rebinding properties are unexpectedly robust against changes in the interactions with close by aromatic residues Trp88 (G8) and Tyr36 (CD1). Molecular dynamics simulations of the CO complex suggest that interactions of the ligand with structural water molecules as well as its rotational freedom play a role in the high reactivity of the ligand and the heme. The slow exchange of ligands between heme and environment may result from a combination of hindered ligand access to the heme pocket by the network of distal aromatic residues, and low escape probability from the pocket.