Structure of human uropepsin at 2.45 angstrom resolution

The molecular structure of human uropepsin, an aspartic proteinase from the urine produced in the form of pepsinogen A in the gastric mucosa, has been determined by molecular replacement using human pepsin as the search model . Crystals belong to space group P2(1)2(1)2(1), with unit-cell parameters a = 50.99, b = 75.56, c = 89.90 Angstrom. Crystallographic refinement led to an R factor of 0.161 at 2.45 Angstrom resolution. The positions of 2437 no n-H protein atoms in 326 residues have been determined and the model contai ns 143 water molecules. The structure is bilobal, consisting of two predomi nantly beta -sheet lobes which, as observed in other aspartic proteinases, are related by a pseudo-twofold axis. A model of the uropepsin-pepstatin co mplex has been constructed based on the high-resolution crystal structure o f pepsin complexed with pepstatin.