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Title:	Active site-directed inhibitors of prolyl oligopeptidase abolishes its conformational dynamics
Author:	López, A.; Herranz-Trillo, F.; Kotev, Martin; Gairí Tahull, Margarida; Guallar, V.; Bernadó Peretó, Pau; Millet Aguilar-Galindo, Òscar; Tarragó Clua, Maria Teresa; Giralt Lledó, Ernest
Other authors:	Universitat de Barcelona
Abstract:	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.
Subject(s):	-Espectroscòpia de ressonància magnètica nuclear -Proteïnes -Nuclear magnetic resonance spectroscopy -Proteins
Rights:	(c) Wiley-VCH, 2016
Document type:	Article Article - Accepted version
Published by:	Wiley-VCH
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