Spontaneous conformational changes in PAI-1

Plasminogen activator inhibitor undergoes spontaneous conformational changes. Using a model-based approach, we introduced mutations that increased the half-life of the active form of the protein by a factor of 20. The mutants were of two types. First, negative charges (glutamate residues) were introduced into the reactive center loop that directly prevent strand insertion. Second, the displacement of the gate was prevented by stablization of the gate region, based on modeling with other serpin structures.