PMC:4504005 / 15846-16757 JSONTXT

{"project":"TEST0","denotations":[{"id":"25982113-79-87-8319021","span":{"begin":207,"end":211},"obj":"[\"20826335\", \"20826335\", \"20826335\"]"}],"text":"The CGRPmut-bound structure explains antagonism by the CGRP receptor-selective small molecule drugs olcegepant and telcagepant. Superposition of the CGRPmut-bound and drug-bound structures (ter Haar et al., 2010) indicated that olcegepant and telcagepant block key interactions of the CGRP C-terminal amide and F37 with the receptor pocket by hydrogen bonding with the CLR T122 main chain at the base of the pocket and packing of their piperidyl moieties against the Trp shelf and G71 (Figures 3C and 3D). Olcegepant also hydrogen bonds with CLR D94, thereby blocking the CGRP T30-CLR D94 interaction (Figure 3C). The position of RAMP1 relative to CLR in the peptide-bound versus drug-bound structures varies such that the drugs appear to favor RAMP1 α2 shifting closer to the small molecule binding sites (Figure 3E), presumably due to drug-RAMP1 interactions including packing against W74 (Figures 3C and 3D)."}

{"project":"2_test","denotations":[{"id":"25982113-20826335-118216123","span":{"begin":207,"end":211},"obj":"20826335"},{"id":"25982113-20826335-118216123","span":{"begin":207,"end":211},"obj":"20826335"},{"id":"25982113-20826335-71076118","span":{"begin":207,"end":211},"obj":"20826335"},{"id":"25982113-20826335-71076118","span":{"begin":207,"end":211},"obj":"20826335"}],"text":"The CGRPmut-bound structure explains antagonism by the CGRP receptor-selective small molecule drugs olcegepant and telcagepant. Superposition of the CGRPmut-bound and drug-bound structures (ter Haar et al., 2010) indicated that olcegepant and telcagepant block key interactions of the CGRP C-terminal amide and F37 with the receptor pocket by hydrogen bonding with the CLR T122 main chain at the base of the pocket and packing of their piperidyl moieties against the Trp shelf and G71 (Figures 3C and 3D). Olcegepant also hydrogen bonds with CLR D94, thereby blocking the CGRP T30-CLR D94 interaction (Figure 3C). The position of RAMP1 relative to CLR in the peptide-bound versus drug-bound structures varies such that the drugs appear to favor RAMP1 α2 shifting closer to the small molecule binding sites (Figure 3E), presumably due to drug-RAMP1 interactions including packing against W74 (Figures 3C and 3D)."}