Serpins exhibit a range of physiological roles and can contribute to certain disease statesdependent on their various conformations. Understanding the mechanisms of the large-scale conformationalreorganizations of serpins may lead to a better understanding of their roles in various cardiovasculardiseases. We have studied the serpin, plasminogen activator inhibitor 1 (PAI-1), in both the active andthe latent state and found that anionic halide ions may play a role in the active-to-latent structural transition.Crystallographic analysis of a stable mutant form of active PAI-1 identified an anion-binding site betweenthe central
![](/images/gifchars/beta2.gif)
-sheet and a small surface domain. A chloride ion was modeled in this site, and its identitywas confirmed by soaking crystals in a bromide-containing solution and calculating a crystallographicdifference map. The anion thus located forms a 4-fold ligated linchpin that tethers the surface domain tothe central
![](/images/gifchars/beta2.gif)
-sheet into which the reactive center loop must insert during the active-to-latent transition.Timecourse experiments measuring active PAI-1 stability in the presence of various halide ions showeda clear trend for stabilization of the active form with F
- > Cl
- > Br
- ![](/images/entities/Gt.gif)
I
-. We propose that the "stickiness"of this pin (i.e.
, the electronegativity of the anion) contributes to the energetics of the active-to-latenttransition in the PAI-1 serpin.