FIGURE 3.

Highlight of residues surrounding positions 158, 296, and 298 in the protease domain in the structures of FVIIa_DVQ (2.2 Å) and wild-type FVIIa (2.0 Å; PDB code 1DAN). A,2F_o – F_c electron density shown at 1σ (blue) and 2σ (red). B, the introduced residues Asp¹⁵⁸ and Gln²⁹⁸ are part of a distinct hydrogen bond network, including water molecule W33 (in red), leading to increased stabilization and burial of the N terminus and establishment of the salt bridge between Ile¹⁵³ and Asp³⁴³. Such a network is not present in the wild-type structure (C) where Met²⁹⁸ occupies a central position via its hydrophobic nature. Note changes in the interface between the Ca²⁺-binding loop (Ca²⁺ shown as a green sphere) and the activation loop via the Val²⁹⁶ mutation, including lack of a hydrogen bond with His²¹¹ and a changed rotamer state of Asp²¹². Root mean square displacements (Cα) of the Ca²⁺-binding loops of the mutant structure versus the wild-type structure were 0.41 Å compared with an overall of 0.43 Å for the heavy chains.