Chi-Lectins: Forms, Functions and Clinical Applications

Abstract

Chitinases (EC.3.2.1.14) hydrolyze the β-1,4-linkages in chitin, an abundant N-acetylglucosamine (GlcNAc) polysaccharide that is a structural component of protective biological matrices of invertebrate such as insect exoskeletons and fungal cell walls. Chitinases cleave chitin and contain the conserved sequence motif DXXDXDXE, in which the glutamate is the catalytic residue. Chitinases are found in species including archaea, bacteria, fungi, plants, and animals. On the basis of sequence homologies, chitinases fall into two groups: families 18 and 19 of glycosyl hydrolases. Members of family 18 employ a substrate-assisted reaction mechanism (van Aalten et al. 2001), whereas those of family 19 adopt a fold-and-reaction mechanism similar to that of lysozyme (Monzingo et al. 1996), suggesting that these families evolved independently to deal with chitin. The glycoside hydrolase 18 (GH18) family of chitinases is an ancient gene family widely expressed in archea, prokaryotes and eukaryotes. Since chitin is an important structural component of pathogens like fungi as well as a constituent of the mammalian diet, a dual function for mammalian chitinases in innate immunity and food digestion has been envisioned (Suzuki et al. 2002; Boot et al. 2005a). Indeed, for human chitotriosidase, an enzyme predominantly expressed by phagocytes, a fungistatic effect has been demonstrated (van Eijk et al. 2005). Several studies have tried to link a common chitotriosidase deficiency to susceptibility for infection by chitin-containing parasites (Bussink et al. 2006). The physiological function of the second mammalian chitinase, acidic mammalian chitinase (AMCase), has attracted considerable attention due to a report linking the protein to the pathophysiology of asthma (Zhu et al. 2004).