Major constraints used in Modeler
GLP-1R Position (A) | GLP-1 Position (B) | Origin for GLP-1R – GLP-1 Constraint | Constrainta (Å) | Reference |
---|---|---|---|---|
ECD; E133; Cγ | A24; Cβ | Bpa24 GLP-1 photoaffinity crosslink. | rAB ≤ 9.0 | Chen et al. 2009c |
TM1; L141;Cδ1 | V16; Cγ1 | Bpa16 GLP-1 photoaffinity crosslink. | rAB ≤ 9.0 | Miller et al. (2011) |
TM1; Y145;Cξ | F12; Cγ | Bpa12 GLP-1 photoaffinity crosslink. | rAB ≤ 6.0 | Chen et al. (2010) |
ECL2; W297;Cη2 | L20; Cγ | Bpa20 GLP-1 photoaffinity crosslink. | rAB ≤ 9.0 | Miller et al. (2011) |
TM2; K197;Nξ | E9; Oε2 | Reciprocal mutagenesis of residues between VIP and VIP-R-1/VIP-R-2 resulting in gain of functionb | rAB ≤ 4.0 | Solano et al. (2001); Vertongen et al. (2001) |
ECL3; R380;Nη2 | D15; Oε2 | Reciprocal mutagenesis of residues between GLP-1 and GLP-1R resulting in gain of function. | rAB ≤ 4.0 | Moon 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.