2wf0

Human BACE-1 in complex with 4-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-8-(2-oxo-1-pyrrolidinyl)-6-quinolinecarboxamideHuman BACE-1 in complex with 4-ethyl-N-((1S,2R)-2-hydroxy-1-(phenylmethyl)-3-(((3-(trifluoromethyl)phenyl)methyl)amino)propyl)-8-(2-oxo-1-pyrrolidinyl)-6-quinolinecarboxamide

Structural highlights 2wf0 is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1tqf, 1xn3, 2vnm, 1m4h, 1xn2, 2fdp, 2viy, 2vie, 2va6, 2vj6, 2viz, 2b8l, 1ym4, 1sgz, 2va5, 1ujk, 2b8v, 1fkn, 1xs7, 2vij, 2va7, 1ym2, 2vj9, 2vkm, 2vnn, 1py1, 1w50, 1ujj, 2vj7, 1w51, 2wf3, 2wf1, 2wf4, 2wez, 2wf2 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. 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 PubMed Inhibition of the aspartyl protease BACE-1 has the potential to deliver a disease-modifying therapy for Alzheimer's disease. We have recently disclosed a series of transition-state mimetic BACE-1 inhibitors showing nanomolar potency in cell-based assays. Amongst them, GSK188909 (compound 2) had favorable pharmacokinetics and was the first orally bioavailable inhibitor reported to demonstrate brain amyloid lowering in an animal model. In this Letter, we describe the reasons that led us to favor a second generation of inhibitors for further in vivo studies. Second generation of BACE-1 inhibitors. Part 1: The need for improved pharmacokinetics.,Charrier N, Clarke B, Cutler L, Demont E, Dingwall C, Dunsdon R, Hawkins J, Howes C, Hubbard J, Hussain I, Maile G, Matico R, Mosley J, Naylor A, O'Brien A, Redshaw S, Rowland P, Soleil V, Smith KJ, Sweitzer S, Theobald P, Vesey D, Walter DS, Wayne G Bioorg Med Chem Lett. 2009 Jul 1;19(13):3664-8. Epub 2009 Apr 17. PMID:19428244 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase

spinqualitylabelsall models 2wf0, resolution 1.60Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image