It Takes Two to Tango: Current Understanding of the Role of M16 Family of Proteases and Their Structural Properties

The M16 protease family comprises metalloendopeptidases, characterized by a unique molecular architecture. The active enzyme molecule is composed of two halves, which together form a structure resembling a clam shell. Although the active site residues are typically located in only one half, both parts are essential for proper enzyme function. The M16 family includes many proteins that are crucial for the physiology of the organism and, therefore, are the subject of intensive research. The flagship examples are insulin-degrading enzyme (IDE), mitochondrial processing peptidases (MPPs), and mitochondrial and chloroplast presequence peptidases (PrePs). The substrates of these enzymes include many biologically important peptides, such as insulin and amyloid β. Therefore, M16 peptidases are considered attractive therapeutic targets, and understanding their structure and mechanism of action is essential for the development of specific and selective modulatory compounds.