Crystal structure of the GPIbα and agkisacucetin complex. (A) Overall structure of the GPIbα-agkisacucetin complex is shown as a cartoon representation (right panel). For the complex, GPIbα is purple, and the α and β chains of agkisacucetin are green and cyan, respectively. A separate GPIbα molecule is shown, with the regions colored for clarity (left panel). (B) Detailed contacts between the GPIbα LRR-6, LRR-7, and LRR-8 regions and the agkisacucetin β chain globular domain. Interacting residues are shown as stick models with hydrogen bonds shown as dotted lines. (C) Detailed contacts between the GPIbα β-switch region and the agkisacucetin β chain globular domain. Interacting residues are shown as stick models with hydrogen bonds shown as dotted lines. (D) Superposition of the GPIbα apo structure (Protein Data Bank identification code 1P9A) (blue) and the GPIbα-agkisacucetin complex (purple). The major conformational change in the β-switch region is indicated by an arrow. (E) Overview of the GPIbα-agkisacucetin complex structure, showing the electrostatic potential of agkisacucetin’s surface. GPIbα is shown in cartoon representation. Blue, positive potential; red, negative potential. (F) Agkisacucetin blocks the interaction between GPIb and thrombin. Fc-tagged GPIb, with or without excess agkisacucetin, was incubated with biotinylated thrombin prebound to streptavidin beads. The streptavidin bead–bound protein samples were analyzed by western blot to examine thrombin and GPIb protein levels using specific antibodies. + and – denote presence and absence of a given protein; +++ denotes excess amounts of protein.