Dissecting factors that contribute to ligand-binding energetics for family 18 chitinases

Inhibition of family 18 chitinases has several interesting applications. To this regard, it is important to understand the dependency of binding energetics with respect to the nature of the ligand as well as the chitinase. We have studied the binding of hexameric N-acetylglucosamine (GlcNAc)6 to both glycon and aglycon subsites in chitinase B (ChiB) of Serratia marcescens and we compare the results with binding of allosamidin to ChiB (glycon subsites only, where products are released) and to chitinase A (ChiA) of S. marcescens (glycon subsites only, where polymeric substrates bind). The image values for the three binding processes were identical within experimental errors (−38 kJ/mol) while binding was driven by different factors, being solvation entropy (−Timage = −52.3 ± 1.5 kJ/mol), conformational entropy (−Timage −45.2 ± 2.0 kJ/mol) , and equal contributions of image and −Timage (−23.4 ± 0.9 and −20.4 ± 3.1 kJ/mol) , respectively.