Interactions of reactive sulfur species with metalloproteins
Andrea Domán,
Éva Dóka,
Dorottya Garai,
Virág Bogdándi,
György Balla,
József Balla,
Péter Nagy
Affiliations
Andrea Domán
Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122, Budapest, Hungary
Éva Dóka
Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122, Budapest, Hungary
Dorottya Garai
Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122, Budapest, Hungary; Kálmán Laki Doctoral School, University of Debrecen, 4012, Debrecen, Hungary
Virág Bogdándi
Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122, Budapest, Hungary
György Balla
Kálmán Laki Doctoral School, University of Debrecen, 4012, Debrecen, Hungary; Department of Pediatrics, Faculty of Medicine, University of Debrecen, 4032, Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, 4012, Debrecen, Hungary
József Balla
Kálmán Laki Doctoral School, University of Debrecen, 4012, Debrecen, Hungary; ELKH-UD Vascular Pathophysiology Research Group, 11003, University of Debrecen, 4012, Debrecen, Hungary; Department of Nephrology, Institute of Internal Medicine, Faculty of Medicine, University of Debrecen, 4012, Debrecen, Hungary
Péter Nagy
Department of Molecular Immunology and Toxicology and the National Tumor Biology Laboratory, National Institute of Oncology, 1122, Budapest, Hungary; Department of Anatomy and Histology, ELKH Laboratory of Redox Biology, University of Veterinary Medicine, 1078, Budapest, Hungary; Chemistry Institute, University of Debrecen, 4012, Debrecen, Hungary; Corresponding author. 7-9 Ráth György street, 1122 Budapest, Hungary.
Reactive sulfur species (RSS) entail a diverse family of sulfur derivatives that have emerged as important effector molecules in H2S-mediated biological events. RSS (including H2S) 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 O2, 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 H2O2 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 H2S-related drug development and the advancement of redox medicine.
