We demonstrate the power of the SFX technique to describe the structure-function relationship in NQO1 for which there was no structural evidence describing the high conformational heterogeneity at the catalytic site

 NQO1 is a flavoenzyme essential for the antioxidant defense system, stabilization of tumor suppressors, and the NAD(P)H-dependent two-electron reduction of a wide variety of substrates, including the activation of quinone-based chemotherapeutics. In addition, alterations in NQO1 function are associated with cancer, Alzheimer's and Parkinson's disease, which makes this enzyme an attractive target for drug discovery. The results reported in this article provide important insight into the conformational heterogeneity of the human NQO1, highlighting the high plasticity of this enzyme in the catalytic site and hence shed light on the molecular basis of NQO1 functional cooperativity.

The article has been published in Lab on a Chip (DOI: 10.1039/D3LC00176H).