Designing molecules that selectively bind to a specific receptor type is often challenging, but can be crucial for different therapeutic purposes.  Both angiotensin II receptors are important drug targets, since the blockade of AT 1 R has anti-hypertensive effects, while the modulation of AT 2 R could be useful for cardioprotection, neuropathic pain relief and the treatment of several other conditions.

Although the AT 1 R and AT 2 R ligands share common scaffolds, the ligand-binding pockets of these two receptors are markedly different, and these differences could be exploited for designing selective ligands. The AT 2 R crystal structures determined in this study improve our understanding of the two types of the human angiotensin receptor and provide new insights into the structural basis for the binding and selectivity of small molecules of therapeutic significance. Our results are therefore expected to facilitate the rational structure-based drug design for improved selectivity.

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