In silico study of anticarcinogenic potential of the selenoprotein BthD from Drosophila melanogaster. Identifying the anticancer peptide CRSUR from the conserved region

Abstract

Drosophila melanogaster is used as a model system in biomedical studies. Selenoprotein is the major biological form of selenium in eukaryotes. Selenoproteins are generally involved in catabolic pathways in bacteria and archaea, whereas it participates in anabolic and antioxidant processes in eukaryotic. In this study, anticancer potential of selenoprotein BthD of D. melanogaster was investigated using bioinformatics methods. Results showed that selenoprotein BthD of D. melanogaster may have dual properties as evident by its orthology with selenoprotein H (SelH) of Homo sapiens and conserved domain of fructokinase-like protein 2 of Vitis vinifera. These dual properties were also revealed in the phylogenetic analysis, while further structural modeling showed that selenoprotein BthD possibly exists as homotetramer in the native functional structure. The anticancer property of selenoprotein BthD was proposed to be by synergy of antioxidant or redox activities of thioredoxin and glutathione reductase (TGR) domain and the signaling function of fructokinase-like protein 2 domain both in Golgi apparatus and cytoplasm, through energy deprivation. The anticancer peptide CRSUR was identified from conserved region of selenoprotein BthD, of which its cyclic form showed potential anticancer properties predictively through E3 ubiquitin-protein ligase regulating NF-kappa-B signaling by unleashing cells for spontaneous formation of the ripoptosome.