Major constraints used in Modeler

GLP-1R Position (A)GLP-1 Position (B)Origin for GLP-1R – GLP-1 ConstraintConstrainta (Å)Reference
ECD; E133; CγA24; CβBpa24 GLP-1 photoaffinity crosslink.rAB ≤ 9.0Chen et al. 2009c
TM1; L141;Cδ1V16; Cγ1Bpa16 GLP-1 photoaffinity crosslink.rAB ≤ 9.0Miller et al. (2011)
TM1; Y145;CξF12; CγBpa12 GLP-1 photoaffinity crosslink.rAB ≤ 6.0Chen et al. (2010)
ECL2; W297;Cη2L20; CγBpa20 GLP-1 photoaffinity crosslink.rAB ≤ 9.0Miller et al. (2011)
TM2; K197;NξE9; Oε2Reciprocal mutagenesis of residues between VIP and VIP-R-1/VIP-R-2 resulting in gain of functionbrAB ≤ 4.0Solano et al. (2001);
Vertongen et al. (2001)
ECL3; R380;Nη2D15; Oε2Reciprocal mutagenesis of residues between GLP-1 and GLP-1R resulting in gain of function.rAB ≤ 4.0Moon et al. (2015)
  • a These distance constraints were estimated from preliminary models that used tyrosine to represent Bpa, since the Oη of the tyrosine is topologically equivalent to the reactive carbon atom of Bpa; a 6-Å constraint was used between the Oη and a suitable point on the target residue.

  • b These residues are conserved between GLP-1R and VPAC-2R. The restraint gives similar results for E9 with K197 and/or R190; if the constraint is used with both residues it can be relaxed to rAB ≤ 5.0 Å or rAB ≤ 6.0 Å.

  • c The potential constraint between Oε1 of E125 and Cα of G35 reported by Chen et al. (2009) (21.5 Å) was not used as the distance in the ECD X-ray structure; this is possibly a constraint to another molecule within an oligomeric array.