Bacterial Active-Site Serine Penicillin-Interactive Proteins and Domains: Mechanism, Structure, and Evolution

Abstract

The bacterial active-site serine penicillin-hydrolyzing and penicillin-binding proteins or domains operate by a serine-ester-linked acyl enzyme mechanism similar to that of the peptidases of the trypsin and subtilisin families. On the basis of known primary and tertiary structures, predictive studies support the view that these proteins or domains form a superfamily of evolutionarily related enzymes. Although--depending on the evolutionary distance--they may have very different amino acid sequences and distinct functional characteristics and specificities, they all would have conserved the same unprecedented type of polypeptide scaffolding. When obtained, complete structural information should provide the necessary tools for the rational design of novel types of inactivators of these important enzyme targets.