title: Structure-function relationship and evolutionary history of the human selenoprotein M (SelM) found over-expressed in hepatocellular carcinoma.
abstract: In humans we know 25 selenoproteins that play important roles in redox regulation, detoxification, immune-system protection and viral suppression. In particular, selenoprotein M (SelM) may function as thiol disulfide oxidoreductase that participates in the formation of disulfide bonds, and can be implicated in calcium responses. However, it presents a redox motif (CXXU), where U is a selenocysteine, and may also function as redox regulator because its decreased or increased expression regulated by dietary selenium alters redox homeostasis. No data are reported in literature about its involvement in cancer but only in neurodegenerative diseases. In this paper we evaluated the SelM expression in two hepatoma cell lines, HepG2 and Huh7, compared to normal hepatocytes. The results suggested its involvement in hepatocellular carcinoma (HCC) as well as its possible use to follow the progression of this cancer as putative marker. The aim of this study has been to analyze the structure-function relationships of SelM. Hence, firstly we studied the evolutionary history of this protein by phylogenetic analysis and GC content of genes from various species. So, we modeled the three-dimensional structure of the human SelM evaluating its energetic stability by molecular dynamics simulations. Moreover, we modeled some of its mutants to obtain structural information helpful for structure-based drug design.
authors: Biochemistry, Biophysics and General Pathology Department and Computational Biology Doctorate, Second University of Naples, Naples, Italy.
authors: Stefano
authors: S
authors: Guariniello
authors: Biochemistry, Biophysics and General Pathology Department and Computational Biology Doctorate, Second University of Naples, Naples, Italy.
authors: Giovanni
authors: G
authors: Colonna
authors: Biochemistry, Biophysics and General Pathology Department and Computational Biology Doctorate, Second University of Naples, Naples, Italy.
authors: Raffaele
authors: R
authors: Raucci
authors: Stazione Zoologica "A. Dohrn", Naples, Italy.
authors: Maria
authors: M
authors: Costantini
authors: Department of Experimental Medicine, Section of Biotechnology and Molecular Biology, Faculty of Medicine, Second University of Naples, Naples, Italy.
authors: Gianni
authors: G
authors: Di Bernardo
authors: Pharmacogenomic Laboratory, Oncology Research Center of Mercogliano (CROM), Istituto Nazionale Per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
authors: Francesca
authors: F
authors: Bergantino
authors: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy.
authors: Giuseppe
authors: G
authors: Castello
authors: Istituto Nazionale Per Lo Studio E La Cura Dei Tumori "Fondazione Giovanni Pascale", IRCCS, Italy. Electronic address: susan.costantini@unina2.it.
authors: Susan
authors: S
authors: Costantini
mesh_terms: D000595:Amino Acid Sequence; D006528:Carcinoma, Hepatocellular / Q000201:enzymology*; D019143:Evolution, Molecular; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D010802:Phylogeny; D051140:Selenoproteins / Q000737:chemistry* / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: C448999:SELM protein, human; D051140:Selenoproteins
keywords: Hepatocellular carcinoma; Interactomic analysis of amino acid residues; Molecular dynamics; Phylogenesis; SelM; Structure