Protein Folding in the Presence of Water-Soluble Cyclic Diselenides with Novel Oxidoreductase and Isomerase Activities

Chembiochem. 2018 Feb 2;19(3):207-211. doi: 10.1002/cbic.201700624. Epub 2017 Dec 29.

Abstract

The protein disulfide isomerase (PDI) family, found in the endoplasmic reticulum (ER) of the eukaryotic cell, catalyzes the formation and cleavage of disulfide bonds and thereby helps in protein folding. A decrease in PDI activity under ER stress conditions leads to protein misfolding, which is responsible for the progression of various human diseases, such as Alzheimer's, Parkinson's, diabetes mellitus, and atherosclerosis. Here we report that water-soluble cyclic diselenides mimic the multifunctional activity of the PDI family by facilitating oxidative folding, disulfide formation/reduction, and repair of the scrambled disulfide bonds in misfolded proteins.

Keywords: diselenides; enzyme models; isomerases; protein folding; selenium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Cell Survival
  • Disulfides / chemistry
  • Disulfides / metabolism
  • Endoplasmic Reticulum / enzymology
  • Eukaryotic Cells / enzymology
  • HEK293 Cells
  • Humans
  • Molecular Structure
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / metabolism*
  • Oxidoreductases / chemistry
  • Oxidoreductases / metabolism*
  • Protein Disulfide-Isomerases / chemistry
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Folding*
  • Solubility
  • Water / chemistry

Substances

  • Disulfides
  • Organoselenium Compounds
  • Water
  • Oxidoreductases
  • Protein Disulfide-Isomerases