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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/125313
Active site-directed inhibitors of prolyl oligopeptidase abolishes its conformational dynamics
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Deciphering conformational dynamics is crucial for understanding the biological functions of proteins and for designing compounds targeting them. In particular, providing an accurate description of microsecond-millisecond motions opens the opportunity for regulating protein-protein interactions (PPIs) by modulating the dynamics of one interacting partner. Here we analyzed the conformational dynamics of prolyl oligopeptidase (POP) and the effects of active-site-directed inhibitors on the dynamics. We used an integrated structural biology approach based on NMR spectroscopy and SAXS experiments complemented by MD simulations. We found that POP is in a slow equilibrium in solution between open and closed conformations, and that inhibitors effectively abolished this equilibrium by stabilizing the enzyme in the closed conformation.
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LÓPEZ ASAMAR, Abraham, et al. Active site-directed inhibitors of prolyl oligopeptidase abolishes its conformational dynamics. ChemBioChem. 2016. Vol. 17, num. 10, pags. 913-917. ISSN 1439-4227. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/125313