A model of the single-chain (sc) prekallikrein (scPK) structure and function is shown. (A) The single-chain tPA crystal structure (pdb:1BDA) is shown with stick diagrams of key residues around the S1 pocket (blue dotted line). The position of the oxyanion hole is indicated by blue spheres that represent the nitrogen atoms of Ser195 and Gly193. The single-chain tPa active S1 pocket reveals Asp194 is stabilized by a salt bridge formed with Lys156. The cyan stick figure represents the side chain of the arginine P1 residue of the tPa inhibitor dansyl-Glu-Gly-Arg-chloromethyl-ketone. (B) Homology model of the S1 pocket of scPK based on the tPA crystal structure where Gln156 forms a hydrogen bond to the Asp194 carboxylate group. (C) The low gear of weak proteolytic activity of the contact system consists of both scPK and scFXII, which constitutively consume each other. Activation of the system requires a stimulus and location to the correct cell membrane to form PKa, FXIIa, and bradykinin (BK).