Human Chitinases: Structure, Function, and Inhibitor Discovery

Abstract

Chitinases are glycosyl hydrolases that hydrolyze the β-(1-4)-linkage of N-acetyl-D-glucosamine units present in chitin polymers. Chitinases are widely distributed enzymes and are present in a wide range of organisms including insects, plants, bacteria, fungi, and mammals. These enzymes play key roles in immunity, nutrition, pathogenicity, and arthropod molting. Humans express two chitinases, chitotriosidase 1 (CHIT1) and acid mammalian chitinase (AMCase) along with several chitinase-like proteins (CLPs). Human chitinases are reported to play a protective role against chitin-containing pathogens through their capability to degrade chitin present in the cell wall of pathogens. Now, human chitinases are gaining attention as the key players in innate immune response. Although the exact mechanism of their role in immune response is not known, studies in recent years begin to relate chitin recognition and degradation with the activation of signaling pathways involved in inflammation. The roles of both CHIT1 and AMCase in the development of various diseases have been revealed and several classes of inhibitors have been developed. However, a clear understanding could not be established due to complexities in the design of the right experiment for studying the role of human chitinase in various diseases. In this chapter, we will first outline the structural features of CHIT1 and AMcase. We will then review the progress in understanding the role of human chitinases in the development of various diseases. Finally, we will summarize the inhibitor discovery efforts targeting both CHIT1 and AMCase.

Keywords: Acid mammalian chitinase; Chitin; Chitinase; Chitotriosidase 1; Inflammation; Inhibitors.