ANALOGOUS INHIBITORS OF ELASTASE DO NOT ALWAYS BIND ANALOGOUSLY

It has been assumed that the structure of a single inhibitor complex i s sufficient to define the available subsites of an enzyme that has a unique binding site and a uniquely defined mode for ligand binding - t he specificity for these subsites can thus be probed by kinetic experi ments. Elastase is an enzyme for which these traditional assumptions, which underlie such structural and kinetic studies, do not hold. Three new crystal structures of elastase complexed to chemically similar in hibitors with similar binding affinities reveal a diversity of binding modes as well as two new subsites on elastase. The existence of multi ple binding sites and different binding modes for such similar inhibit ors indicates that researchers must proceed with caution when using ki netics to map out protein subsites.