Fig. 3: Effects on X dimerization by Hit 1.
From: Regulation of cadherin dimerization by chemical fragments as a trigger to inhibit cell adhesion
a Hydrogen–deuterium exchange ratio of two peptides 134–140 and 137–147 as a function of time. The region of these peptides is colored in magenta in the structure of MEC12, X dimer (PDB ID; 4zmq). Chain A of X dimer is colored in sky blue; chain B in pink. b Structure of the complex of the X dimer and Hit 1. Hit 1 (in the sphere, orange) is bound in the cavity around Y140 of each monomeric chain and at the intersection of EC2 domains. The pink or sky blue or black arrows show Hit 1 that binds to chain A or chain B or at the intersection of EC2 domains, respectively. c Structural change caused by the binding of Hit 1. Hit 1-bound X dimer is aligned to the apo-state X dimer (PDB ID; 4zmq, black). The angle of EC1 to EC2 is flatter compared to that in the apo-state X dimer. The arrows indicate the movement of domains. d Hydrogen bonds disrupted by the structural change that occurs upon Hit 1 binding. In the apo-state X dimer, K14-A138’ hydrogen bond is shown in the dotted line. In Hit 1-bound X dimer, the K14-A138’ hydrogen bond is disrupted. Amino acid residues from chain A are shown in sky blue, those from chain B are in pink. e Size measurement using SEC-MALS. The WT X dimer trace is in blue, the K14A mutant trace is in red. N = 1. f Frequency histogram of the distance between a hydrogen bond donor and an acceptor of the pairs of K14-A138’ and K14’-A138 observed in the MD simulations of the apo-state X dimer (PDB ID; 4zmq). The black dotted lines represent the distances observed in the crystal structure of Hit 1-bound X dimer we obtained in this study.
