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Updated: May 13, 2026
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Monitoring the Reductive and Oxidative Half-Reactions of a Flavin-Dependent Monooxygenase using Stopped-Flow Spectrophotometry
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Chloroquine binding reveals flavin redox switch function of quinone reductase 2
Kevin K K Leung1, Brian H Shilton
1Department of Biochemistry, University of Western Ontario, London, Ontario N6A 5C1, Canada.
The Journal of Biological Chemistry
|March 9, 2013
Summary
Quinone reductase 2 (NQO2) structural changes were revealed upon binding antimalarial drugs. This reveals NQO2
Area of Science:
- Biochemistry
- Structural Biology
- Enzymology
Background:
- Quinone reductase 2 (NQO2) is an FAD-dependent enzyme.
- It is the sole human target for antimalarial drugs primaquine (PQ) and chloroquine (CQ).
Purpose of the Study:
- To investigate structural differences between oxidized and reduced NQO2.
- To elucidate the structural basis for PQ and CQ inhibition.
Main Methods:
- X-ray crystallography was employed.
- Structures of oxidized NQO2 in complex with PQ and CQ were determined at 1.4 Å resolution.
Main Results:
- Chloroquine (CQ) preferentially binds to reduced NQO2.
- Reduction of NQO2-CQ crystals induced a space group change and decreased unit cell dimensions.
- A new CQ binding mode and active site loop closure were observed upon reduction.
Conclusions:
- This study presents the first structure of reduced quinone reductase.
- Reduction of the FAD cofactor and inhibitor binding cause global structural changes in NQO2.
- These findings support a role for NQO2 as a flavin redox switch.
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