Abstract: Methods of using monoclinic crystals of human beta-secretase (BACE) having unit cell dimensions of a, b, and c, wherein a is about 81±20 ? to about 101 ?, b is 103±20 ?, c is 100±20 ?, and ?=?=90°, and ? is 105°±10° for crystals of symmetry P21 and a=73.1, b=105.1, c=50.5 ? and ? is 94.8° for crystals of C2 symmetry in drug screening assays comprising selecting a potential modifier by adding the potential modifiers to an aqueous mixture of the crystal and detecting a measure of binding, such that the potential modifier that binds is selected as a potential drug.

Abstract: The x-ray crystal structure of human BACE or BACE-like proteins is useful for solving the structure of other molecules or molecular complexes, and identifying and/or designing potential modifiers of human BACE activity.

Abstract: An inhibitor bound form of human beta secretase, also known as memapsin 2 and BACE, particularly in a glycosylated form as expressed in Chinese hamster ovary (CHO), HEK293 cells, or in insect cells as part of a Baculovirus expression system has been crystallized, and the three dimensional x-ray crystal structure has been solved to 3.2 ? resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of human beta secretase activity.