Fig. P1.

The malaria vector uses a unique anticoagulant strategy. The crucial procoagulant enzyme, thrombin (gray ellipsoid), has two positively charged surface regions (blue) important for the interaction with substrates and other macromolecular partners. Natural procoagulant substrates (e.g., fibrinogen) bind across thrombin’s active site (dashed rectangle) and are cleaved between the P1 and P1′ residues, leading to thrombus formation (Left). Conversely, anophelin binds to thrombin in an unexpected reverse orientation (relative to natural substrates), blocking its catalytic activity in a unique way and effectively impairing blood coagulation (Right). N and C denote the N and C termini of the polypeptide chain, respectively.