Hypothetical model of the productive thrombin·FVa2 complex. The model was generated based on the current structure of FPR–α-thrombin·FVa2 and that of S195A thrombin bound to a fragment from the PAR1 ectodomain that includes the activation cleavage site (PDB code 3LU9).³⁹  Factor V residues Leu⁷⁰⁶ (P₄) to Phe⁷¹¹ (P₂′) were modeled according to the conformation of the equivalent PAR1 sequence, and the 2 polypeptide fragments were then extended following standard peptide geometries. The well-defined active-site– and exosite I–binding regions are highlighted in green. Notice that the relatively large distance between these 2 peptides (∼ 40 Å between Cα atoms of residues Glu⁶⁷² and Leu⁷⁰⁶) necessarily implies that the intervening sequence has to adopt a rather extended conformation, running close to the thrombin surface. The spatial proximity of clusters of acidic residues, Asp⁶⁵⁹-Asp⁶⁶³ and Glu⁷¹⁹-Glu⁷²², in the Michaelis complex is also noteworthy. The side chain of the arginine residue targeted by APC (Arg⁶⁷⁹) is also shown, as well as Tyr⁶⁹⁸, which could contact basic residues at the edge of exosite II, especially if sulfated.