Abstract
Human BACE, also known as beta-secretase, shows promise as a potential therapeutic target for Alzheimer's disease. We determined the apo structure of BACE to 1.75 A, and a structure of a hydroxyethylamine inhibitor complex derived by soaking. These show significant active-site movements compared to previously described BACE structures. Additionally, the structures reveal two pockets that could be targeted by structure-based drug design.
MeSH terms
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Amines / chemistry*
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Amines / metabolism
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Amyloid Precursor Protein Secretases
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Animals
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Aspartic Acid Endopeptidases
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Binding Sites
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Crystallography, X-Ray
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Drug Design
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Endopeptidases / chemistry*
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Endopeptidases / metabolism
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Enzyme Inhibitors / chemistry*
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Enzyme Inhibitors / metabolism
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Humans
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Hydrogen Bonding
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Mice
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Models, Molecular
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Molecular Sequence Data
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Molecular Structure
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Protein Structure, Tertiary*
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Temperature
Substances
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Amines
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Enzyme Inhibitors
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Amyloid Precursor Protein Secretases
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Endopeptidases
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Aspartic Acid Endopeptidases
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BACE1 protein, human
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Bace1 protein, mouse