Journal: Neurochemistry international

Article Title: Identification of the Benztropine Analog [ 125 I]GA II 34 Binding Site on the Human Dopamine Transporter

doi: 10.1016/j.neuint.2018.08.008

Figure Lengend Snippet: Structures of (A) cocaine, (B) benztropine, (C) [125I]GA II 34, (D) [125I]MFZ 2–24, and (E) [125I]RTI 82 showing the shared tropane nitrogen pharmacophore and orientation of IAP moiety. (F) Autoradiogram of hDAT photoaffinity labeled with 15 nM [125I]GA II 34 in the absence or presence of 10 μM mazindol followed by immunoprecipitation with Ab16. Molecular mass marker (kDa) is shown on the right.

Article Snippet: In contrast, the cocaine-bound dDAT crystal structure revealed a fully open-to out structure, which could follow from the presence of negative Glu residues incapable of forming ionic or salt bridges at the homologous positions. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 4. caption a7 Computational Docking and Molecular Dynamics Simulations. (A) RosettaLigand docking of GA II 34 to hDAT model with pre-MD pose in (yellow) and post-MD (150 ns simulation) pose in (light blue).

Techniques: Labeling, Immunoprecipitation, Marker

Journal: Neurochemistry international

Article Title: Identification of the Benztropine Analog [ 125 I]GA II 34 Binding Site on the Human Dopamine Transporter

doi: 10.1016/j.neuint.2018.08.008

Figure Lengend Snippet: Computational Docking and Molecular Dynamics Simulations. (A) RosettaLigand docking of GA II 34 to hDAT model with pre-MD pose in (yellow) and post-MD (150 ns simulation) pose in (light blue). Notable side chains are shown as lines in the respective color. Na (purple) and Cl (green) in the post-MD model are shown as spheres. Distances between the tropane N and D79 side chain, the reactive azido N and the L80 side chain and the outergate residues R85 and D476 are shown as magenta dashed lines (Pymol, Schrodinger). The TM6 helix is not shown for clarity. (B) 2D plot of post-MD GA II 34 (A) where polar, aliphatic, and charged residues are color coded and point toward the part of the molecule they coordinate. (C) DAT side chains within 5Å of the additional phenyl-fluoro arm of GA II 34 (yellow) overlayed MFZ 2–34-DAT complex (brown) from Krout et al. 2017. (D) Stereo image overlay of post MD GA II 34 (blue) with cocaine (magenta) from Wang et al. 2015.

Article Snippet: In contrast, the cocaine-bound dDAT crystal structure revealed a fully open-to out structure, which could follow from the presence of negative Glu residues incapable of forming ionic or salt bridges at the homologous positions. fig ft0 fig mode=article f1 fig/graphic|fig/alternatives/graphic mode="anchored" m1 Open in a separate window Figure 4. caption a7 Computational Docking and Molecular Dynamics Simulations. (A) RosettaLigand docking of GA II 34 to hDAT model with pre-MD pose in (yellow) and post-MD (150 ns simulation) pose in (light blue).

Techniques: