Structural Characterization of Alzheimer DNA Promoter Sequences from the Amyloid Precursor Gene in the Presence of Thioflavin T and Analogs

Understanding DNA–ligand binding interactions requires ligand screening, crystallization, and structure determination. In order to obtain insights into the amyloid peptide precursor (APP) gene–Thioflavin T (ThT) interaction, single crystals of two DNA sequences 5′-GCCCACCACGGC-3′ (PDB 8ASK) d(CCGGGGTACCCCGG)2 8ASH) were grown in presence ThT or its analogue 2-((4-(dimethylamino)benzylidene)amino)-3,6-dimethylbenzo[d]thiazol-3-ium iodide (XRB). Both structures solved by molecular replacement. case 8ASK, space group was H3 with unit cell dimensions a = b 64.49 Å, c 46.19 Å. Phases obtained using model generated X3DNA. The novel 12-base-pair B-DNA did not have extra density for ligand. 14-base-pair A-DNA bound analog XRB isomorphous previously apo-DNA 5WV7 (space P41212 41.76 88.96 Å). Binding slightly changes DNA’s buckle parameters at CpG regions. Comparison conformations molecule: alone indicates that results from freedom rotation aromatic rings.