10.1371/journal.pone.0107809.g004 John Gatfield John Gatfield Celia Mueller Grandjean Celia Mueller Grandjean Daniel Bur Daniel Bur Martin H. Bolli Martin H. Bolli Oliver Nayler Oliver Nayler Modeling of macitentan (A) and bosentan (B) binding to the active site of the ET<sub>A</sub> receptor. Public Library of Science 2014 target occupancy ETA receptor binding pocket 355A dissociation kinetics ETA receptor residues ERA activity mutation L 322A ETA receptor dissociation rate NMR analysis binding mode macitentan potencies acid point mutations Muscle cells ETA receptor variants endothelin binding site Distinct ETA Receptor Binding Mode ambrisentan antagonist activity bosentan potency Mutation R 326Q endothelin receptor antagonists novel ERA macitentan ERA interaction site ETA receptor 2014-09-16 03:04:28 Figure https://plos.figshare.com/articles/figure/_Modeling_of_macitentan_A_and_bosentan_B_binding_to_the_active_site_of_the_ET_A_receptor_/1171683 <p>The amino acid residues predicted to contact macitentan and/or bosentan are grouped into the categories “nearest neighbors”, “ERA charge interaction” and “extended ERA binding pocket”. (C) Conformations of macitentan (red) and bosentan (green) bound to ET<sub>A</sub> as proposed by molecular modeling. Relevant structural differences are (1) the different head groups, (2) the length of the central rigid axis spanning over the head group and either one (macitentan) or two (bosentan) pyrimidines, (3) the presence or absence of the 5-bromo-pyrimidine stacking onto the core pyrimidine.</p>