High quality structure of cleaved PAI-1-stab

• Published in: Journal of structural biology Vol. 165; no. 2; pp. 126 - 132
• Main Authors: Dewilde, M., Strelkov, S.V., Rabijns, A., Declerck, P.J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-02-2009
• Subjects: Catalytic Domain; Crystal structure; Crystallography, X-Ray; Humans; Models, Molecular; Molecular Conformation; Molecular Structure; Mutation; PAI-1; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen Activator Inhibitor 1 - physiology; Plasminogen activator inhibitor-1; Protein Binding; Protein Conformation; Protein Structure, Tertiary; Rational drug design; Serpin; Serpins - chemistry; PAI-1; Serpin; Plasminogen activator inhibitor-1; Crystal structure; Rational drug design
• ISSN: 1047-8477; 1095-8657
• DOI: 10.1016/j.jsb.2008.11.001

Here we report the crystal structure of a stablilized plasminogen activator inhibitor-1 variant (PAI-1-N150H-K154T-Q301P-Q319L-M354I (PAI-1-stab)) that shows a cleavage within the reactive centre loop. The new structure is of superior quality compared to the previously determined structure of the cleaved PAI-1-A335P mutant. We present a detailed comparison of the two structures and also compare them with the structure of the active PAI-1-stab. The structural data give important insights into the working mechanism of PAI-1 and also explain the role of various stabilizing mutations.