2v00

X-ray crystal structure of endothiapepsin complexed with compound 1

spinqualitylabelsall models 2v00, resolution 1.55Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2v00 is a 1 chain structure with sequence from Cryphonectria parasitica. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.55Å Ligands: ACT, GOL, V15 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function CARP_CRYPA 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 Fragment-based lead generation was applied to find novel small-molecule inhibitors of beta-secretase (BACE-1), a key target for the treatment of Alzheimer's disease. Fragment hits coming from a 1D NMR screen were characterized by BIAcore, and the most promising compounds were soaked into protein crystals to help the rational design of more potent hit analogues. Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead against BACE-1, and the accompanying paper in this journal describes how these were optimized to a lead series of nanomolar inhibitors.1. Discovery of a novel warhead against beta-secretase through fragment-based lead generation.,Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Pepsin

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