Cholesterol oxidases: A study of nature's approach to protein design

Cholesterol oxidases are important as clinical reagents, potential larvicides, and tools in cell biology, and they are implicated in bacterial pathogenesis. Here we review chemical aspects of their function. We describe our current structural and mechanistic understanding of the type I and II cholesterol oxidases, our identification of an NH-π hydrogen bond motif for stabilization of reduced flavins, our structural hypothesis of how O ₂ gains access to the flavin, and our present understanding of type I cholesterol oxidase-lipid bilayer interactions.