The present invention provides a crystal of human beta-secretase (BACE) having monoclinic space group symmetry C2, in a representative example, comprising a unit cell having dimensions of a, b, and c, wherein a is about 53 .ANG. to about 103 .ANG., b is about 85 .ANG. to about 125 .ANG., c is about 40 .ANG. to about 60 .ANG., and .alpha.=.gamma.=90.degree., and .beta. is about 85.degree. to about 105.degree., and in a preferred example, comprising unit cell dimensions as follows: a is 73.1 .ANG., b is 105.1 .ANG., c is 50.5 .ANG., and .alpha.=.gamma.=90.degree., and .beta. is 94.8, wherein the Matthews coefficient of said crystal is 2.1 .ANG./Da with 42% solvent, and wherein said crystal diffracts to 1.7 .ANG. resolution.