stabilizing native alcohols in the pocket through hydrogen bonding. Tagging GIRK2 channels with a hydroxy-benzyl moiety, however, did not activate the channel, indicating that a small increase in side-chain volume was incompatible with channel activation. Importantly, simply attaching alcohol-like compounds to the βD-βE loop was not sufficient for chemical activation, since tagging S246C situated approximately 7 angstroms from L257 was ineffective at promoting channel activation. Thus, proximity to the pocket and hydrophobicity are key features for chemical-dependent activation of GIRK2 channels through the alcohol pocket.
