Belsomra: Difference between revisions

Belsomra assumes a conformation similar to that of a horseshoe when binding to the [http://www.nature.com/nbt/journal/v32/n11/fig_tab/nbt.3028_F2.html orthosteric binding pocket] of either <scene name='74/746099/Orx1/3'>orexin receptor 1</scene> or <scene name='74/746099/Suvorexant/5'>orexin receptor 2</scene>. Through steric hindrance, this horseshoe conformation halts transmembrane domain movement by making contact with the alpha-helices of all transmembrane domains except for the first one upon entering the binding site of the receptor. <ref name="six"> doi: 10.1038/nature14035 </ref>. Types of interactions between Belsomra and both orexin receptor subtypes include Van Der Waals interactions, aromatic packing via the pi bonds of aromatic amino acids, and hydrogen bonding. The most significant hydrogen bond occurs between the amide of Belsomra and the side chain of Asn318 (Orexin receptor 1), and the side chain of Asn324 (Orexin receptor 2) <ref name="six" />. Water molecules also play a role in hydrogen bonding via formation of bridges between the Belsomra drug itself and the orexin receptors’ Asn324 and <scene name='74/746099/His350/2'>His350</scene>. <ref name="six" />. Structural differences of the two orexin receptors’ binding sites involve only two amino acids: <scene name='74/746099/Thr135_orx2/1'>Thr135</scene> in receptor 2 is <scene name='74/746099/Ala127_orx1/1'>Ala127</scene> in receptor 1, while <scene name='74/746099/Thr111_orx2/1'>Thr111</scene> in receptor 2 is <scene name='74/746099/Ser103_orx1/1'>Ser103</scene> in receptor 1. <ref name="six" /><ref>doi:10.1038/nsmb.3198</ref>.