A substrate-based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen.

@article{Jgot2011ASA,
  title={A substrate-based approach to convert SerpinB1 into a specific inhibitor of proteinase 3, the Wegener's granulomatosis autoantigen.},
  author={Gwenhael J{\'e}got and Chrystelle Derache and Sandrine Castella and Hichem Lahouassa and Elodie Pitois and Marie Lise Jourdan and Eileen Remold-O'Donnell and Christine Kellenberger and Francis L Gauthier and Brice Korkmaz},
  journal={FASEB journal : official publication of the Federation of American Societies for Experimental Biology},
  year={2011},
  volume={25 9},
  pages={3019-31}
}
The physiological and pathological functions of proteinase 3 (PR3) are not well understood due to its close similarity to human neutrophil elastase (HNE) and the lack of a specific inhibitor. Based on structural analysis of the active sites of PR3 and HNE, we generated mutants derived from the polyvalent inhibitor SerpinB1 (monocyte/neutrophil elastase inhibitor) that specifically inhibit PR3 and that differ from wt-SerpinB1 by only 3 or 4 residues in the reactive center loop. The rate constant… CONTINUE READING