THE STRUCTURE OF CHITINASES AND PROSPECTS FOR STRUCTURE-BASED DRUG DESIGN

Many fungi, including pathogenic strains, require proper chitin metabo lism to assure normal cell wall replication. Chitinase hydrolyzes chit in; inhibition of endogenous chitinases or application of extracellula r chitinases can disrupt fungal division. It is possible that chitinas e inhibitors could be used as antifungal agents. We have solved the X- ray structure of a class II chitinase from barley and proposed a mecha nism of action. The enzyme has a structural core similar to lysozyme a nd probably acts in a similar catalytic manner. The enzyme structure c an, in principle, be used to identify small molecules that will bind a vidly to the active site and act as inhibitors. Those inhibitors that embody transition state geometry are likely to be particularly effecti ve.