Figure 7

Mechanisms to destabilize the intramolecular interaction between kringle-1 and the protease domain thereby shifting the equilibrium toward the open form. (a) In prothrombin, Trp547 (5EDM, yellow stick) forms a face-to-face interaction with the aromatic side chain of Tyr93 (red stick). In the structure of the Na⁺-bound thrombin²⁷ (1SG8, magenta stick) Trp547 relocates promoting opening of the active site. (b) Binding of argatroban (magenta stick) into the active site of prethrombin-2³⁴ (4RN6, green stick) requires relocation of both Tyr93 and Trp547 (c) In the structure of prethrombin-1³⁰ (3NXP, cyan stick) and prethrombin-2²³ (3SQE, gray stick), Trp547 further collapses into the active site.