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Instead of occupying the orthosteric binding pocket where peptide or small molecule agonists generally bind, the high-resolution cryo-EM map demonstrates that compound 2 is covalently bonded to C347 6.36b (Wootten numbering in superscript 37 ) and mounted on the membrane-facing surface of the cytoplasmic end of TM6, providing solid structural evidence of a unique binding site for the ago-allosteric modulator (Fig