Hemeproteins as targets for sulfide species

Abstract

The binding of sulfide to ferric hemeproteins has been described in more than 40 systems, including native proteins, mutants, and model systems. Mechanisms of sulfide binding to ferric hemeproteins have been examined by a combination of kinetic and computational experiments. The distal control of the association process, dissected into the migration of the ligand to the active site and the binding event, reveals that neutral hydrogen sulfide (H2S) reaches the active site and is the predominant binding ligand, while the HSis excluded by the protein matrix. Experiments with model compounds, devoid of a protein scaffold, reveal that both H2S and HS¯ can bind the ferric heme if accessing the site. A critical role of the proximal ligand in the prevention of the metal-centered reduction has been experimentally assessed. For metmyoglobin and methemoglobin, the coordination of sulfide leads to noncanonical functions: sulfide storage and its oxidative detoxification have been evidenced under physiological and excess sulfide concentrations, respectively.