Fig 3. Divergent interactions of SB269652 with EL2 and TM5 in D2R and D3R.
IleEL2.51 in D2R forms direct hydrophobic interactions with the cyclohexyl linker of SB269652 and Leu2.64 (A), while the aligned SerEL2.51 in D3R cannot (B), resulting in different orientations of IleEL2.52 in these two receptors. In addition, the divergence in EL2 and near the proline-kink of TM5 (position 5.52) contributes to the different interactions of the serines on top of TM5 with the cyano group of SB269652 (see text). Molecular graphics was generated using PyMOL Molecular Graphics System (version 1.7.6.5, Schrödinger, LLC).