METHODS FOR USING KDOP AND KDOP SYNTHASE INHIBITORS FOR THE TREATMENT OF BACTERIAL INFECTION

摘要

The two crystal structures of KDOPS that we present here illustrate the value of protein crystal structural analysis for characterizing the enzymatic reaction mechanism of KDOPS. Mechanistic hypotheses have underscored certain specifics of the interaction between the enzyme and the substrate, and these features in turn have provided further clarification of the details of the enzymatic reaction. The structure and function of 3-deoxy-D-manno-2-octulosonate-8-phosphate (KDOSP) synthase, discussed herein provide a new target antibacterial drugs. KDO8P synthase catalyzes the synthesis of a unique sugar that is a required component of the outer membrane lipopolysaccharides of Gram-negative bacteria. The enzyme activity is required for the full viability of Gram-negative bacteria. Overall these disclosures provide a new method for developing new drugs, and methods of using the same to treat infections caused by bacteria that are resistant to conventional drugs.