title: Identification of small molecular inhibitors for Ero1p by structure-based virtual screening.
abstract: Ero1p, using molecular oxygen as its preferred terminal electron acceptor, promotes disulfide bond formation by interaction with protein disulfide isomerase. Dysfunction of Ero1p leads to strong activation of the unfolded protein response and marked loss of cell viability. However, modest attenuation of Ero1p improves the fitness of yeast challenged with high levels of protein misfolding in their endoplasmic reticulum stress. Partial inhibition of Ero1p is hence of great significance. In the present paper, a docking-based virtual screening method was performed to identify inhibitors of Ero1p and 12 hits were successfully obtained from 81 purchased compounds with micromolar inhibition against Ero1p. Particularly, six of the hits demonstrated remarkable potency with IC(50)<30μM and held the prospect of becoming lead compounds. Then the interaction modes were analyzed for further lead optimization.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Chu
authors.forename: Xianjun
authors.initials: X
authors.lastname: Chen
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Yun
authors.initials: Y
authors.lastname: Tang
mesh_terms: D001665:Binding Sites; D003198:Computer Simulation; D030562:Databases, Protein; D005182:Flavin-Adenine Dinucleotide / Q000737:chemistry; D006023:Glycoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D006023:Glycoproteins; D008562:Membrane Glycoproteins; D029701:Saccharomyces cerevisiae Proteins; D054852:Small Molecule Libraries; D005182:Flavin-Adenine Dinucleotide; C405327:ERO1A protein, human; D010088:Oxidoreductases; D050862:Oxidoreductases Acting on Sulfur Group Donors; C113186:ERO1 protein, S cerevisiae