Structural Studies on Intact Clostridium botulinum Neurotoxins Complexed with Inhibitors Leading to Drug Design

摘要

This is an annual report in no cost extension period. In this period we have identified several compounds via virtual screening. These compounds include small molecules transition state analogues and benzimidazoles. Since there is a commonality in the active site architecture, we have developed a strategy to identify inhibitors that will act on more than one serotype. Most importantly, we have determined the structure of botulinum neurotoxin type E which shows a different domain organization than either BoNT/A or B.