What is the structure of proprotein processing enzymes, and can we identify activators and inhibitors of these enzymes?
Using recombinant protein expression and protein purification we can produce milligram quantities of recombinant convertases as well as of the two endogenous binding proteins. The following questions are currently being addressed using these materials: a. Determination of the crystal structure of a prohormone convertase We are collaborating with the crystallography group of Dr. Manuel Than in Jena, Germany to crystallize convertases. Our work on mouse furin resulted in the publication of the structure of the first mammalian convertase in mid-2003 (Henrich et al, Nature Structural Biology 10,520-526). We would like now to obtain the structure of other convertases, such as PC1/3, as well as of convertase-inhibitor complexes (PC2 and 7B2). Model of the Furin Substrate Binding Site, Courtesy of Stefan Henrich and Manuel Than b. Identification of convertase inhibitors. Our collaboration with Drs. Houghten and Appel of the Torrey Pines Institute for Molecular Studies provides us with natural
