AT 3-dimensional structure indicating the location of residue 229. (A) Ribbon overview of native AT complexed with heparin, showing the location of residue 229 (magenta) and key serpin areas (see “Structural analysis”). (B) Close-up of the AT Phe229 area (ball-and-stick rendering). The residues surrounding Phe229 are shown in yellow. Part of the reactive center loop (RCL) is shown in red. Phe229 (magenta) is shown in the same orientation as in panel A. The free space available around Phe229 is symbolized by small dashed circles (white). The Phe229Leu substitution increased the amount of free space that might be filled by local structural reorganizations; alternatively, a destabilizing cavity may remain in the structure. Reorganization and/or cavity formation could induce structural changes that propagate toward the RCL and the breach area itself. In the absence of structural adjustment, a number of residues (mainly Glu377, Met252, Gln254, Tyr253, and Ser230, underlined) could clash with the Leu side chain.