ABSTRACT
Proteolytic enzymes are potentially hazardous to their protein environment, and thus their activity must be carefully controlled. Proteolytic activity can be regulated by modulating the synthesis or degradation of the enzyme or necessary cofactors or via interactions with activators or inhibitors (1). Living organisms use inhibitors as a major tool in regulating the proteolytic activity of proteinases. Indeed, proteinases and their respective inhibitors are found in almost every system where proteolysis occurs. Among the four major classes of proteolytic enzymes — serine, cysteine, aspartic, and metalloproteinases — special attention must be given to the class of cysteine proteinases, especially to the papain-like cysteine proteinase that forms the largest subfamily among them. Papain-like proteinases are widely expressed throughout the animal and plant kingdoms and have also been identified in viruses and bacteria (2). Mammalian papain-like cysteine proteinases are known as thiol-dependent cathepsins (3). According to the human genome database (https://www.genome. ad.jp/dbget/dbget), 11 cathepsins are expressed in the human genome as papain-like enzymes. Currently, evidence suggests that papain-like cathepsins carry out specific functions in extracellular matrix turnover, antigen
presentation, and processing events in the human body (2). Consequently, investigations of papain-like proteinase inhibitors have been designed to reduce pathogen infectivity, prevent muscular dystrophies and joint destruction, and inhibit tumorigenesis and metastasis. In addition to the commercial applications of the inhibitors for controlling the deterioration of protein gels during food processing (4,5), understanding their properties for regulation of the proteinases would be helpful in therapeutic applications, in which they can represent viable drug candidate for major diseases such as osteoporosis, arthritis, immune-related diseases, tumors, cancers, and a wide variety of parasitic infections.
