Mapping the Substrate Recognition Landscapes of Metalloproteases Using Comprehensive Mutagenesis

Protease specificity is controlled by exosites, which capture and orient the substrate, and the active site, which binds substrate residues near the P1–P1′ scissile bond and catalyzes peptide hydrolysis. Techniques used to identify critical contact points between a protease and its substrate can be time consuming and labor-intensive. Screening tools such as phage display have been revitalized with the emergence of high-throughput sequencing …