Revised definition of substrate binding sites of papain-like cysteine proteases

A review of kinetic and structural data has enabled us to reconsider the definition of substrate binding sites in papain-like cysteine proteases. Only three substrate binding sites, S2, S1 and S1', involve main as well as side chain contacts between substrate and enzyme residues. Interactions between the enzymes and the substrate P3 and P2' residues are based on side chains (an exception is cathepsin B which is a carboxydipeptidase), so their interaction surface spreads over a relatively wide area. The location and definition of substrate binding sites beyond S3 and S2' is even more questionable.