Structure-function prediction of alpha_(2A)-, alpha_(2B)-, and alpha_(2C)-adrenoceptors using homology model assisted antagonist binding study

摘要

alpha_(2A)-, alpha_(2B), and alpha_(2C)--adrenoceptors belong to the rhodopsin-like G-protein coupled receptors family. They are integral membrane proteins typified by a bundle of seven transmembrane helices. 50 % of the currently available drugs in the market target G-protein coupled receptors. Crystal structure of alpha_(2A)-, alpha_(2B), and alpha_(2C)--adreno-ceptors are not yet solved. We performed homology modeling of the human alpha_(2A)-, alpha_(2B), and alpha_(2C)--adrenoceptor subtypes based on the crystal structure of the beta_2-adrenergic receptor. Molecular docking studies of five different antagonists toward these receptors revealed receptor subtype selectivity, and which in turn potentially guide in the rational design of subtype selective antagonists.