Quinone Reductase 2 (NQO2) is a fascinating enzyme that we believe has a role in cell signalling. As an enzyme, NQO2 catalyzes the reduction of quinones, which can be toxic to cells. However, NQO2 is highly unusual because it has evolved to use the conventional dihydronicotinamide coenzymes very inefficiently, and instead exhibits a preference for dihydronicotinamide riboside (NRH). NQO2 interacts with many drugs and bioactive compounds, including melatonin, resveratrol, imatinib and other kinase inhibitors, as well as chloroquine and other anti-malarials. Based on these observations, we believe that NQO2 is involved in the cellular response to these drugs.
Our goal is to understand the cellular function of NQO2, and we are doing this by a combination of structure-function studies and experiments in mammalian cells. One of our most exciting discoveries is that when NQO2 is reduced and binds the anti-malarial drug chloroquine (yellow in the dimeric NQO2 structure below), it undergoes a change in conformation and dynamics indicating that NQO2 may function as a “flavin redox switch”. The reduced flavin co-factor is shown with green carbons.
