Crystallization and structure determination of glycosylated human beta secretase, an enzyme implicated in alzheimer's disease
AssigneePfizer Inc.
InventorsTimothy Benson, Jim Durbin, D. Prince
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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 Å 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.
Claims19
A method for crystallizing a human beta secretase molecule or molecular complex comprising:
- preparing a purified human beta secretase in the presence of an inhibitor;
- and
- crystallizing the human beta secretase molecule or molecular complex from a solution comprising the purified human beta secretase and the inhibitor, wherein the solution has a pH of at most about 6.0.
Dependencies are inferred from the claim text.