Fig. 5.

Structural differences between agonist and antagonist state of MR. (A) Intrahelix hydrogen bond network within H8 of native (gray) and T870L mutant (cyan) hMR LBD. An extra hydrogen bond is formed between the hydroxyl of T870 and amide carbonyl of F866. Asterisk indicates the backbone carbonyl group of the residue (i) that forms a hydrogen bond with the residue (i+4) in native LBD, which is absent in the T870L mutant. (B) Hydrophobic network mediated through L742 in hMR-T870L. H1 remains helical in hMR-T870L H1 but uncoils in native LBD. Hydrophobic interactions are showed as dotted lines. (C) The missing hydrophobic network in both native (gray) and L742A-T870L double mutant (dark cyan). In both cases, due to the absence of effective mediators L870 or L742, the hydrophobic network is not maintained.