Inhibition in multicopper oxidases: a critical review

Multicopper oxidases (MCO), such as laccases and bilirubin oxidases, are catalysts of wide interest in a range of biotechnological applications, especially bioremediation and energy transduction. Many of these processes take place in the presence of dissolved species, particularly halides, at concentrations high enough to inhibit the catalytic activity of MCOs. Despite this, MCO inhibition is rarely considered the focus of reviews on these enzymes. This review critically analyses the scientific literature on modes of MCO inhibition and current hypotheses on the structural origins of inhibition. The article provides a comprehensive overview of what is known from the different techniques applied to the study of MCO inhibition. These techniques include solution-based enzymatic assays, electrochemical methodologies, various spectroscopic approaches, X-ray crystallography and computational analyses. This review highlights gaps in the literature, identifies nine challenges to accurately benchmarking MCO inhibition and gives recommendations to address these challenges and to interpret published data on the subject.