title: Crystal structure of the complex of plasminogen activator inhibitor 2 with a peptide mimicking the reactive center loop.
abstract: 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.
authors.affiliation: Initiative in Biomolecular Structure, School of Physics, University of New South Wales, Sydney New South Wales 2052, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Jankova
authors.forename: S J
authors.initials: SJ
authors.lastname: Harrop
authors.forename: D N
authors.initials: DN
authors.lastname: Saunders
authors.forename: J L
authors.initials: JL
authors.lastname: Andrews
authors.forename: K C
authors.initials: KC
authors.lastname: Bertram
authors.forename: A R
authors.initials: AR
authors.lastname: Gould
authors.forename: M S
authors.initials: MS
authors.lastname: Baker
authors.forename: P M
authors.initials: PM
authors.lastname: Curmi
mesh_terms: D018360:Crystallography, X-Ray; D004583:Electrons; D004926:Escherichia coli / Q000378:metabolism; D017353:Gene Deletion; D005998:Glycine / Q000737:chemistry; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D010455:Peptides / Q000737:chemistry*; D017396:Plasminogen Activator Inhibitor 2 / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D015843:Serpins / Q000737:chemistry; D013912:Threonine / Q000737:chemistry
chemical_list: D010455:Peptides; D017396:Plasminogen Activator Inhibitor 2; D011994:Recombinant Proteins; D015843:Serpins; D013912:Threonine; D005998:Glycine