A small molecule chaperone rescues the stability and activity of a cancer-associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro

Emilia Strandback, Wolf-Dieter Lienhart, Altijana Hromic-Jahjefendic, Benjamin Bourgeois, Anja Högler, Daniel Waltenstorfer, Andreas Winkler, Klaus Zangger, Tobias Madl, Karl Gruber, Peter Macheroux

Research output: Contribution to journalArticlepeer-review


NAD(P)H:quinone oxidoreductase 1 (NQO1) is a human FAD-dependent enzyme that plays a crucial role in the antioxidant defense system. A naturally occurring single-nucleotide polymorphism (NQO1*2) in the NQO1 gene leads to an amino acid substitution (P187S), which severely compromises the activity and stability of the enzyme. The NQO1*2 genotype has been linked to a higher risk for several types of cancer and poor survival rate after anthracycline-based chemotherapy. In this study, we show that a small molecular chaperone (N-(2-bromophenyl)pyrrolidine-1-sulfonamide) repopulates the native wild-type conformation. As a consequence of the stabilizing effect, the enzymatic activity of the P187S variant protein is strongly improved in the presence of the molecular chaperone in vitro.

Original languageEnglish
Pages (from-to)424-438
JournalFEBS Letters
Issue number3
Publication statusPublished - 2020

Fields of Expertise

  • Human- & Biotechnology

Cite this