Structure-function relationship and evolutionary history of the human selenoprotein M (SelM) found over-expressed in hepatocellular carcinoma

Stefano Guariniello, Giovanni Colonna, Raffaele Raucci, Maria Costantini, Gianni Di Bernardo, Francesca Bergantino, Giuseppe Castello, Susan Costantini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)447-456
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1844
Issue number2
DOIs
Publication statusPublished - Feb 2014

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Keywords

  • Hepatocellular carcinoma
  • Interactomic analysis of amino acid residues
  • Molecular dynamics
  • Phylogenesis
  • SelM
  • Structure

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Analytical Chemistry
  • Molecular Biology

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