Translations:Discovery and development of angiotensin receptor blockers/12/en

Binding pockets

Fig 1. Losartan receptor binding

Ang II binds to AT₁ receptors via various binding sites. The primary binding site is at the extracellular region of the AT₁ receptor where Ang II interacts with residues in the N-terminus of the AT₁ receptor and its first and third extracellular loops. The transmembrane helices also contribute to the binding via the C-terminal carboxyl group that interacts with Lys¹⁹⁹ in the upper part of helix 5 of the receptor; see figure 1 for details.
The ionic bridge formed between Lys¹⁹⁹ and the carboxyl terminal group of the Phe⁸ residue of Ang II is most likely stabilized by the Trp²⁵³ residue. In addition, Phe²⁵⁹ and Asp²⁶³ in transmembrane helix 6 and Lys¹⁰² and Ser¹⁰⁵ in the outer region of transmembrane helix 3 have also been implicated in Ang II binding. This region may possibly participate in the stabilization of the receptor's ratification and in the formation of the intramembrane binding pocket.