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Crystal structure of the complex of plasminogen activator inhibitor 2 with a 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-A resolution. The structure shows the relaxed state serpin structure with a prominent six-stranded beta-sheet. Clear electron density is seen for all residues in the peptide. The P1 residue of the 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 stressed-to-relaxed state (S --> R) transition in PAI-2 can be modeled as the relative motion between a quasirigid core domain and a smaller segment comprising helix hF and beta-strands s1A, s2A, and s3A. A comparison of the Ramachandran plots of the stressed and relaxed state PAI-2 structures reveals the location of several hinge regions connecting these two domains. The hinge regions cluster in three locations on the structure, ensuring a cooperative S --> R transition. We hypothesize that the hinge formed by the conserved Gly(206) on beta-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 region of PAI-2.

Type Journal
ISBN 0021-9258 (Print)
Authors Jankova, L.;Harrop, S. J.;Saunders, D. N.;Andrews, J. L.;Bertram, K. C.;Gould, A. R.;Baker, M. S.;Curmi, P. M. :
Published Date 2001-01-01
Published Volume 276
Published Issue 46
Published Pages 43374-82
Status Published in-print
URL link to publisher's version