Complement protein Factor D plays an important role in the alternative pathway of the complement system. Inhibitors for Factor D have potential application in treatment of adult respiratory syndrome (ARDS) and autoimmune diseases such as rheumatoid arthritis. The phase I aim of this proposal was to determine three-dimensional structure of Factor by X-ray crystallographic methods. We have determined the three-dimensional structure by a combination of molecular replacement model and multiple isomorphous replacement methods. The structure has been refined to 2 Angstrom resolution. The objective of the work described in this proposal is to design and synthesize specific inhibitors for Factor D using a structure-based drug design process.
