3qbh | pdb_00003qbh

Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors

spinqualitylabelsall models 3qbh, resolution 2.24Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3qbh is a 3 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: QBH Related: 3pi5 Gene: BACE, BACE1, KIAA1149 (HUMAN) Activity: Memapsin 2, with EC number 3.4.23.46 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [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. Publication Abstract from PubMed This Letter describes the de novo design of non-peptidic hydroxyethylamine (HEA) inhibitors of BACE-1 by elimination of P-gp contributing amide attachments. The predicted binding mode of the novel cyclic sulfone HEA core template was confirmed in a X-ray co-crystal structure. Inhibitors of sub-micromolar potency with an improved property profile over historic HEA inhibitors resulting in improved brain penetration are described. Structure based design, synthesis and SAR of cyclic hydroxyethylamine (HEA) BACE-1 inhibitors.,Rueeger H, Rondeau JM, McCarthy C, Mobitz H, Tintelnot-Blomley M, Neumann U, Desrayaud S Bioorg Med Chem Lett. 2011 Apr 1;21(7):1942-7. Epub 2011 Feb 15. PMID:21388807 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase 3D structures

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