4gid: Difference between revisions
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | [https://www.uniprot.org/uniprot/BACE1_HUMAN BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref> | ||
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== Publication Abstract from PubMed == | |||
The structure-based design, synthesis, and X-ray structure of protein-ligand complexes of exceptionally potent and selective beta-secretase inhibitors are described. The inhibitors are designed specifically to interact with S(1)' active site residues to provide selectivity over memapsin 1 and cathepsin D. Inhibitor 5 has exhibited exceedingly potent inhibitory activity (K(i) = 17 pM) and high selectivity over BACE 2 (>7000-fold) and cathepsin D (>250000-fold). A protein-ligand crystal structure revealed important molecular insight into these selectivities. These interactions may serve as an important guide to design selectivity over the physiologically important aspartic acid proteases. | |||
Structure-Based Design of Highly Selective beta-Secretase Inhibitors: Synthesis, Biological Evaluation, and Protein-Ligand X-ray Crystal Structure.,Ghosh AK, Venkateswara Rao K, Yadav ND, Anderson DD, Gavande N, Huang X, Terzyan S, Tang J J Med Chem. 2012 Sep 6. PMID:22954357<ref>PMID:22954357</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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==See Also== | ==See Also== | ||
Latest revision as of 02:56, 21 November 2024
Structure of beta-secretase complexed with inhibitor
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