Comparison of binding modes of dabigatran to Fab and thrombin. aDabi-Fab mimics structural features of thrombin to bind dabigatran (same color scheme as in Figure 3, thrombin is colored in pale green, H-bonds and aromatic interactions are indicated as dotted lines in green and blue, respectively). The dabigatran complex structure of aDabi-Fab and thrombin is displayed in the left and right panels, respectively. (A-B) The benzamidine moiety of dabigatran binds into a cavity of the proteins and forms a bidentate salt bridge to H:Asp35 and Asp189, respectively. The salt bridge is further stabilized by a conserved hydrogen bonding pattern with L:His96 and H:Asp100D or with a water molecule and Gly219. (C-D) The benzimidazole moiety of dabigatran interacts by π-stacking with L:Tyr27D and Trp60D, respectively. The pyridine ring of dabigatran interacts with a T-shaped π-stacking with H:Trp52 and Trp215, respectively. (E-F) The catalytic triad of thrombin is formed by His57, Asp102, and Ser195. The Fab contains in the same region an arrangement of L:Tyr27D, L:Ser91, and L:Thr92 that is not able to convey proteolytic activity.