Crystal structure of the complex of plasminogen activator inhibitor 2 witha peptide mimicking the reactive center loop

The structure of the serpin, plasminogen activator inhibitor type-2 (PAI-2) , in a complex with a peptide mimicking its reactive center loop (RCL) has been determined at 1.6-Angstrom resolution. The structure shows the relaxed state serpin structure with a prominent six-stranded beta -sheet. Clear el ectron density is seen for all residues in the peptide. The P1 residue of t he peptide binds to a well defined pocket at the base of PAI-2 that may be important in determining the specificity of protease inhibition. The stress ed-to-relaxed state (S --> R) transition in PAI-2 can be modeled as the rel ative motion between a quasirigid core domain and a smaller segment compris ing helix hF and beta -strands s1A, s2A, and s3A. A comparison of the Ramac handran plots of the stressed and relaxed state PAI-2 structures reveals th e location of several hinge regions connecting these two domains. The hinge regions cluster in three locations on the structure, ensuring a cooperativ e S --> R transition. We hypothesize that the hinge formed by the conserved Gly(206) on P-strand s3A in the breach region of PAI-2 effects the S --> R transition by altering its backbone torsion angles. This torsional change is due to the binding of the P14 threonine of the RCL to the open breach re gion of PAI-2.