Prothrombin structures. Prothrombin is a multidomain protein that adopts closed (A) and open (B) states. It comprises the N-terminal Gla-domain (blue), 2 kringles (kringle 1 [K1], red; kringle 2 [K2], green), and a serine protease domain (SP, yellow). The X-ray crystal structures of the prothrombin mutant proTCC (Protein Data Bank Identifier: 6C2W,²⁶  left panel) and proTΔ154-167(Protein Data Bank Identifier: 5EDM,³⁴  right panel) have been solved recently. Mutation of residues S101 and A470 to cysteine in proTCC stabilizes the closed form. The location of these 2 residues is shown in cyan. Conversely, mutation of residue Y93 to alanine in the mutant proTY93A, deletion of 14 of 26 residues of Lnk2 in the mutant proTΔ154-167, or addition of argatroban stabilizes the open form. The location of these residues is shown in magenta. The Gla-domain of both structures has been slightly modified from the original structures and adopts the calcium-bound, physiologically relevant conformation.⁴⁷