Figure 7.

Effect of H₁R sequence variants N198S and Y108C on doxepin binding. (A) A hydrogen bond (blue dotted line) is formed between N198^5.461 and doxepin. N198^5.461 and doxepin are shown in stick representation and colored according to the type of element (carbons of N198^5.461 and doxepin are colored in gray and green, respectively). (B) In the N198S variant, a weaker hydrogen bond (thin dotted line) is formed due to the shorter serine sidechain. (C) Interaction between Y108^3.33 and doxepin. The interaction partners are shown in stick representation, and the volume of the atoms is additionally indicated as transparent spheres. (D) The smaller sidechain of the Y108C variant results in a loss of hydrophobic interactions with doxepin.