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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, HERRANZ-TRILLO, F., KOTEV, Martin, GAIRÍ TAHULL, Margarida, GUALLAR, Victor, BERNADÓ PERETÓ, Pau, MILLET AGUILAR-GALINDO, Òscar, TARRAGÓ CLUA, Maria teresa, GIRALT LLEDÓ, Ernest. Active site-directed inhibitors of prolyl oligopeptidase abolishes its conformational dynamics. _ChemBioChem_. 2016. Vol. 17, núm. 10, pàgs. 913-917. [consulta: 27 de gener de 2026]. ISSN: 1439-4227. [Disponible a: https://hdl.handle.net/2445/125313]