Interactions of reactive sulfur species with metalloproteins

Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in H(2)S-mediated biological events. RSS (including H(2)S) can exert their biological roles via widespread interactions with metalloproteins. Metalloproteins are essential components along the metabolic route of oxygen in the body, from the transport and storage of O(2), through cellular respiration, to the maintenance of redox homeostasis by elimination of reactive oxygen species (ROS). Moreover, heme peroxidases contribute to immune defense by killing pathogens using oxygen-derived H(2)O(2) as a precursor for stronger oxidants. Coordination and redox reactions with metal centers are primary means of RSS to alter fundamental cellular functions. In addition to RSS-mediated metalloprotein functions, the reduction of high-valent metal centers by RSS results in radical formation and opens the way for subsequent per- and polysulfide formation, which may have implications in cellular protection against oxidative stress and in redox signaling. Furthermore, recent findings pointed out the potential role of RSS as substrates for mitochondrial energy production and their cytoprotective capacity, with the involvement of metalloproteins. The current review summarizes the interactions of RSS with protein metal centers and their biological implications with special emphasis on mechanistic aspects, sulfide-mediated signaling, and pathophysiological consequences. A deeper understanding of the biological actions of reactive sulfur species on a molecular level is primordial in H(2)S-related drug development and the advancement of redox medicine.