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 journalArticleResearchpeer-review

Abstract

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
JournalFEBS letters
Early online date12 Oct 2019
DOIs
Publication statusPublished - 30 Oct 2019

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Fields of Expertise

  • Human- & Biotechnology

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