6dr5 | pdb_00006dr5

X-ray crystallographic structure of a covalent trimer derived from A-beta 17_36 containing the I31Chg point mutation

spinqualitylabelsall models 6dr5, resolution 2.08Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6dr5 is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MPD NonStd Res: CHG, MEA, ORN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Soluble oligomers of the beta-amyloid peptide, Abeta, are associated with the progression of Alzheimer's disease. Although many small molecules bind to these assemblies, the details of how these molecules interact with Abeta oligomers remain unknown. This paper reports that crystal violet, and other C3 symmetric triphenylmethane dyes, bind to C3 symmetric trimers derived from Abeta17-36. Binding changes the color of the dyes from purple to blue, and causes them to fluoresce red when irradiated with green light. Job plot and analytical ultracentrifugation experiments reveal that two trimers complex with one dye molecule. Studies with several triphenylmethane dyes reveal that three N, N-dialkylamino substituents are required for complexation. Several mutant trimers, in which Phe19, Phe20, and Ile31 were mutated to cyclohexylalanine, valine, and cyclohexylglycine, were prepared to probe the triphenylmethane dye binding site. Size exclusion chromatography, SDS-PAGE, and X-ray crystallographic studies demonstrate that these mutations do not impact the structure or assembly of the triangular trimer. Fluorescence spectroscopy and analytical ultracentrifugation experiments reveal that the dye packs against an aromatic surface formed by the Phe20 side chains and is clasped by the Ile31 side chains. Docking and molecular modeling provide a working model of the complex in which the triphenylmethane dye is sandwiched between two triangular trimers. Collectively, these findings demonstrate that the X-ray crystallographic structures of triangular trimers derived from Abeta can be used to guide the discovery of ligands that bind to soluble oligomers derived from Abeta. Repurposing Triphenylmethane Dyes to Bind to Trimers Derived from Abeta.,Salveson PJ, Haerianardakani S, Thuy-Boun A, Yoo S, Kreutzer AG, Demeler B, Nowick JS J Am Chem Soc. 2018 Sep 19;140(37):11745-11754. doi: 10.1021/jacs.8b06568. Epub, 2018 Sep 6. PMID:30125493 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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