Molecular modeling of rFXIII-A₂* bound to the extended fibrin αC fragment residues 328-402. (A) FXIII-A₂ in its nonactive form complete with activation peptides (AP). (B) Activated FXIII-A₂ (half open) following cleavage of the activation peptide. (C) Activated FXIII-A₂ (half open) shown bound to the fibrin αC fragment 328-402. rFXIII-A₂* cross-linking site AαQ366 is shown adjacent to 1 rFXIII-A₂* active site C314 residue (CC, yellow ball). The rest of the αC fragment up to AαQ328 is unbound. (D) Activated FXIII-A₂ (fully open) following cleavage of the activation peptide. (E) Activated FXIII-A₂ (fully open) following cleavage of the activation peptide, shown bound to the fibrin αC fragment 328-402. Both AαQ366 and AαQ328 rFXIII-A₂* cross-linking sites are adjacent to both rFXIII-A₂* active site C314 residues (yellow ball). The crystal structures (PDB codes 1F13 and 2Q3Z) are shown as ribbons. Molecular modeling was performed using the Maestro Modeling suite from Schrodinger Inc. using an analogous approach to that previously described by Komaromi et al.³⁵