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Structure of human NAD(P) H:quinone oxidoreductase in complex with N-(2-bromophenyl)pyrrolidine-1-sulfonamideStructure of human NAD(P) H:quinone oxidoreductase in complex with N-(2-bromophenyl)pyrrolidine-1-sulfonamide
Structural highlights
Function[NQO1_HUMAN] The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis. Publication Abstract from PubMedNAD(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. A small molecule chaperone rescues the stability and activity of a cancer-associated variant of NAD(P)H:quinone oxidoreductase 1 in vitro.,Strandback E, Lienhart WD, Hromic-Jahjefendic A, Bourgeois B, Hogler A, Waltenstorfer D, Winkler A, Zangger K, Madl T, Gruber K, Macheroux P FEBS Lett. 2020 Feb;594(3):424-438. doi: 10.1002/1873-3468.13636. Epub 2019 Oct, 30. PMID:31605637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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