Elan Pharmaceuticals, Inc.

Pharmacia & Upjohn Company

Pfizer Corporation

Timothy Earl Benson

Donald Bryan Prince

Jim D Durbin

Daisy Danielle Woods

D Danielle Woods

D Bryan Prince

Alfredo Giuseppe Tomasselli

Thomas L Emmons

Melissa S Harris

The x-ray crystal structure of 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 BACE activity.

Ligand screening method using a crystal of beta secretase

Methods of using monoclinic crystals of human beta-secretase (BACE) having unit cell dimensions of a, b, and c, wherein a is about 81&#xb1;20 &#x212b; to about 101 &#x212b;, b is 103&#xb1;20 &#x212b;, c is 100&#xb1;20 &#x212b;, and &#x3b1;=&#x3b3;=90&#xb0;, and &#x3b2; is 105&#xb0;&#xb1;10&#xb0; for crystals of symmetry P2and a=73.1, b=105.1, c=50.5 &#x212b; and &#x3b2; is 94.8&#xb0; 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.

Methods of using crystals of beta amyloid cleaving enzyme (BACE)

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 &#x212b; 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.

Method for crystallizing human beta secretase in complex with an inhibitor

Crystallization and structure determination of glycosylated human beta secretase, an enzyme implicated in alzheimer's disease

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 &#x212b; to about 103 &#x212b;, b is about 85 &#x212b; to about 125 &#x212b;, c is about 40 &#x212b; to about 60 &#x212b;, and &#x3b1;=&#x3b3;=90&#xb0;, and &#x3b2; is about 85&#xb0; to about 105&#xb0;, and in a preferred example, comprising unit cell dimensions as follows: a is 73.1 &#x212b;, b is 105.1 &#x212b;, c is 50.5 &#x212b;, and &#x3b1;=&#x3b3;=90&#xb0;, and &#x3b2; is 94.8, wherein the Matthews coefficient of said crystal is 2.1 &#x212b;/Da with 42% solvent, and wherein said crystal diffracts to 1.7 &#x212b; resolution.

Crystal of human beta secretase having monoclinic space group symmetry C2 and methods for crystallization thereof

Crystals of unliganded beta secretase and/or beta secretase-like proteins and the use thereof

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.

Crystal of HIV protease-cleaved human beta secretase and method for crystallization thereof

Crystallization and structure determination of glycosylated human beta secretase, an enzyme implicated in Alzheimer's disease

An unliganded form ofNAD synthetase (NadE) has been crystallized, and the three-dimensional x-ray crystal structure has been solved to 2.3 &#x212b; resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors ofNadE activity.

Crystallization and structure determination of Staphylococcus aureus NAD synthetase

An unliganded form of thymidylate kinase ( TMK) has been crystallized, and the three dimensional x-ray crystal structure has been solved to 2.3 &angst; resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of TMK activity.

Crystallization and structure determination of Staphylococcus aureus thymidylate kinase

The substrate free form of UDP-N-acetylenolpyruvylglucosamine reductase ( MurB) has been crystallized, and the three dimensional x-ray crystal structure has been solved to 2.3 &angst; resolution. The x-ray crystal structure is useful for solving the structure of other molecules or molecular complexes, and designing inhibitors of MurB.

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Chesterfield, MO, United States of America

Timothy Earl Benson