6FY4

Structure of human NAD(P) H:quinone oxidoreductase in complex with N-(2-bromophenyl)pyrrolidine-1-sulfonamide

Summary for 6FY4

• Entry DOI: 10.2210/pdb6fy4/pdb
• Descriptor: NAD(P)H dehydrogenase [quinone] 1, FLAVIN-ADENINE DINUCLEOTIDE, N-(2-bromophenyl)pyrrolidine-1-sulfonamide (3 entities in total)
• Functional Keywords: flavoprotein ligand complex quinone reduction oxidative stress drug metabolism, oxidoreductase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 4
• Total formula weight: 127077.84

Authors

Gruber, K.,Hromic, A. (deposition date: 2018-03-10, release date: 2019-03-20, Last modification date: 2024-01-17)

Primary citation

Strandback, E.,Lienhart, W.D.,Hromic-Jahjefendic, A.,Bourgeois, B.,Hogler, 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., 594:424-438, 2020

PubMed 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.

PubMed: 31605637
DOI: 10.1002/1873-3468.13636

Experimental method

X-RAY DIFFRACTION (2.76 Å)