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The critical nature of this exact architecture is highlighted by specific mutagenesis: mutating Tyr138 to alanine (Y138A) totally disrupts this hydrophobic stacking and drastically decreases the potency of retatrutide, verifying that the physical, spatial proximity of these two aromatic rings is a cornerstone of GCGR engagement

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doi: 10.1016/j.immuni.2011.07.010 107 MaXJTianDYXuDYangDFZhuHFLiangZHet al

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