6eqm

Crystal Structure of Human BACE-1 in Complex with CNP520Crystal Structure of Human BACE-1 in Complex with CNP520

Structural highlights 6eqm is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.35Å Ligands: 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 The beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) initiates the generation of amyloid-beta (Abeta), and the amyloid cascade leading to amyloid plaque deposition, neurodegeneration, and dementia in Alzheimer's disease (AD). Clinical failures of anti-Abeta therapies in dementia stages suggest that treatment has to start in the early, asymptomatic disease states. The BACE-1 inhibitor CNP520 has a selectivity, pharmacodynamics, and distribution profile suitable for AD prevention studies. CNP520 reduced brain and cerebrospinal fluid (CSF) Abeta in rats and dogs, and Abeta plaque deposition in APP-transgenic mice. Animal toxicology studies of CNP520 demonstrated sufficient safety margins, with no signs of hair depigmentation, retina degeneration, liver toxicity, or cardiovascular effects. In healthy adults >/= 60 years old, treatment with CNP520 was safe and well tolerated and resulted in robust and dose-dependent Abeta reduction in the cerebrospinal fluid. Thus, long-term, pivotal studies with CNP520 have been initiated in the Generation Program. The BACE-1 inhibitor CNP520 for prevention trials in Alzheimer's disease.,Neumann U, Ufer M, Jacobson LH, Rouzade-Dominguez ML, Huledal G, Kolly C, Luond RM, Machauer R, Veenstra SJ, Hurth K, Rueeger H, Tintelnot-Blomley M, Staufenbiel M, Shimshek DR, Perrot L, Frieauff W, Dubost V, Schiller H, Vogg B, Beltz K, Avrameas A, Kretz S, Pezous N, Rondeau JM, Beckmann N, Hartmann A, Vormfelde S, David OJ, Galli B, Ramos R, Graf A, Lopez Lopez C EMBO Mol Med. 2018 Sep 17. pii: emmm.201809316. doi: 10.15252/emmm.201809316. PMID:30224383 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase 3D structures

spinqualitylabelsall models 6eqm, resolution 1.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image