PMC:4504005 / 28311-29227 JSONTXT

{"project":"TEST0","denotations":[{"id":"25982113-122-130-8319048","span":{"begin":122,"end":126},"obj":"[\"20188075\", \"20188075\", \"20188075\"]"},{"id":"25982113-144-152-8319049","span":{"begin":144,"end":148},"obj":"[\"24199627\", \"24199627\", \"24199627\"]"}],"text":"RAMP1 W84 and RAMP2 E101 were previously identified as key residues for CGRP and AM function, respectively (Moore et al., 2010; Watkins et al., 2014). These data are explained by how these residues augment the binding site pocket (Figures 7A and 7B). Apparently, packing of the CGRP F37 and AM Y52 phenyl rings against the CLR Trp shelf and G71 is insufficient for strong binding. RAMP1 W84 or RAMP2 E101 is required to complete the pocket to enable strong “anchoring” of the peptide C termini. RAMP2 R97 and E105 also augment the pocket, but the R97A and E105A mutants did not diminish AM potency. These data along with the peptide swap data indicate that the RAMP2 E101-Y52 hydrogen bond is the crucial AM anchoring contact. Ionic interactions of AM K46 and RAMP2 E101/E105 do not appear to be significant. The main role of AM K46 thus appears to be intramolecular packing against Y52 and contacting the Trp shelf."}

{"project":"2_test","denotations":[{"id":"25982113-20188075-118216149","span":{"begin":122,"end":126},"obj":"20188075"},{"id":"25982113-20188075-118216149","span":{"begin":122,"end":126},"obj":"20188075"},{"id":"25982113-24199627-118216150","span":{"begin":144,"end":148},"obj":"24199627"},{"id":"25982113-24199627-118216150","span":{"begin":144,"end":148},"obj":"24199627"},{"id":"25982113-20188075-71076132","span":{"begin":144,"end":148},"obj":"20188075"},{"id":"25982113-20188075-71076132","span":{"begin":144,"end":148},"obj":"20188075"},{"id":"25982113-24199627-71076132","span":{"begin":144,"end":148},"obj":"24199627"},{"id":"25982113-24199627-71076132","span":{"begin":144,"end":148},"obj":"24199627"}],"text":"RAMP1 W84 and RAMP2 E101 were previously identified as key residues for CGRP and AM function, respectively (Moore et al., 2010; Watkins et al., 2014). These data are explained by how these residues augment the binding site pocket (Figures 7A and 7B). Apparently, packing of the CGRP F37 and AM Y52 phenyl rings against the CLR Trp shelf and G71 is insufficient for strong binding. RAMP1 W84 or RAMP2 E101 is required to complete the pocket to enable strong “anchoring” of the peptide C termini. RAMP2 R97 and E105 also augment the pocket, but the R97A and E105A mutants did not diminish AM potency. These data along with the peptide swap data indicate that the RAMP2 E101-Y52 hydrogen bond is the crucial AM anchoring contact. Ionic interactions of AM K46 and RAMP2 E101/E105 do not appear to be significant. The main role of AM K46 thus appears to be intramolecular packing against Y52 and contacting the Trp shelf."}