3duy
From Proteopedia
Crystal structure of human beta-secretase in complex with NVP-AFJ144
Structural highlights
FunctionBACE1_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.[1] [2] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe hydroxyethylene octapeptide inhibitor OM99-2 served as starting point to create the tripeptide inhibitor 1 and its analogues 2a and b. An X-ray co-crystal structure of 1 with BACE-1 allowed the design and syntheses of a series of macrocyclic analogues 3a-h covalently linking the P1 and P3 side-chains. These inhibitors show improved enzymatic potency over their open-chain analogue. Inhibitor 3h also shows activity in a cellular system. Structure-based design and synthesis of macrocyclic peptidomimetic beta-secretase (BACE-1) inhibitors.,Machauer R, Veenstra S, Rondeau JM, Tintelnot-Blomley M, Betschart C, Neumann U, Paganetti P Bioorg Med Chem Lett. 2009 Mar 1;19(5):1361-5. Epub 2009 Jan 19. PMID:19195886[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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