4DUS
Structure of Bace-1 (Beta-Secretase) in complex with N-((2S,3R)-1-(4-fluorophenyl)-3-hydroxy-4-((6'-neopentyl-3',4'-dihydrospiro[cyclobutane-1,2'-pyrano[2,3-b]pyridin]-4'-yl)amino)butan-2-yl)acetamide
Summary for 4DUS
Entry DOI | 10.2210/pdb4dus/pdb |
Related | 3RSV |
Descriptor | Beta-secretase 1, IODIDE ION, GLYCEROL, ... (5 entities in total) |
Functional Keywords | hydrolase, aspartyl protease, app, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor |
Biological source | Homo sapiens (human) |
Cellular location | Membrane; Single-pass type I membrane protein: P56817 |
Total number of polymer chains | 1 |
Total formula weight | 47378.58 |
Authors | Sickmier, E.A. (deposition date: 2012-02-22, release date: 2012-10-10, Last modification date: 2024-10-09) |
Primary citation | Kaller, M.R.,Harried, S.S.,Albrecht, B.,Amarante, P.,Babu-Khan, S.,Bartberger, M.D.,Brown, J.,Brown, R.,Chen, K.,Cheng, Y.,Citron, M.,Croghan, M.D.,Graceffa, R.,Hickman, D.,Judd, T.,Kriemen, C.,La, D.,Li, V.,Lopez, P.,Luo, Y.,Masse, C.,Monenschein, H.,Nguyen, T.,Pennington, L.D.,Miguel, T.S.,Sickmier, E.A.,Wahl, R.C.,Weiss, M.M.,Wen, P.H.,Williamson, T.,Wood, S.,Xue, M.,Yang, B.,Zhang, J.,Patel, V.,Zhong, W.,Hitchcock, S. A Potent and Orally Efficacious, Hydroxyethylamine-Based Inhibitor of beta-Secretase. ACS Med Chem Lett, 3:886-891, 2012 Cited by PubMed Abstract: β-Secretase inhibitors are potentially disease-modifying treatments for Alzheimer's disease. Previous efforts in our laboratory have resulted in hydroxyethylamine-derived inhibitors such as 1 with low nanomolar potency against β-site amyloid precursor protein cleaving enzyme (BACE). When dosed intravenously, compound 1 was also shown to significantly reduce Aβ40 levels in plasma, brain, and cerebral spinal fluid. Herein, we report further optimizations that led to the discovery of inhibitor 16 as a novel, potent, and orally efficacious BACE inhibitor. PubMed: 24900403DOI: 10.1021/ml3000148 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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