STRUCTURAL BASIS OF SUBSTRATE-SPECIFICITY IN THE SERINE PROTEASES

Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biologi cal function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in pr oviding strength and specificity of binding, the extent to which bindi ng subsites are interdependent, and the roles of polypeptide chain fle xibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why spe cificity modification can be either straightforward or complex, depend ing on the particular system.