Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Strandback, E; Lienhart, WD; Hromic-Jahjefendic, A; Bourgeois, B; Högler, A; Waltenstorfer, D; Winkler, A; Zangger, K; Madl, T; Gruber, K; Macheroux, P.
A small molecule chaperone rescues the stability and activity of a cancer-associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro.
FEBS Lett. 2020; 594(3):424-438
Doi: 10.1002/1873-3468.13636
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- Co-Autor*innen der Med Uni Graz
- Bourgeois Benjamin Michel Rene
- Madl Tobias
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- 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. © 2019 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Drug Evaluation, Preclinical -
- Enzyme Activation - drug effects
- Enzyme Stability - drug effects
- Ligands -
- Molecular Docking Simulation -
- Mutant Proteins - antagonists & inhibitors
- Mutant Proteins - chemistry
- Mutant Proteins - genetics
- Mutant Proteins - metabolism
- Mutation -
- NAD(P)H Dehydrogenase (Quinone) - antagonists & inhibitors
- NAD(P)H Dehydrogenase (Quinone) - chemistry
- NAD(P)H Dehydrogenase (Quinone) - genetics
- NAD(P)H Dehydrogenase (Quinone) - metabolism
- Neoplasms - genetics
- Protein Conformation -
- Find related publications in this database (Keywords)
- cancer
- chemical chaperone
- chemotherapeutics
- quinone
- single-nucleotide polymorphism