COMPARISON OF HOMOLOGY MODELS WITH THE EXPERIMENTAL STRUCTURE OF A NOVEL SERINE-PROTEASE

A model structure of the human complement enzyme factor D was built ba sed on homology with related serine proteases. A molecular-replacement solution of the factor D crystal structure employing the homology mod el refined without manual intervention to an R factor of 0.249 with 2. 4 Angstrom native diffraction data. A multiple isomorphous replacement (MIR) electron-density map was subsequently produced, leading to a mo del refined at 2.0 Angstrom resolution to an R factor of 0.188. A homo logy model built with commercial modeling software was subjected to th e same procedure. Comparisons of the homology models with the final re fined MIR structure are presented. Major discrepancies were found in c ritical active-site regions.