Journal
CHEMBIOCHEM
Volume 17, Issue 10, Pages 913-917Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201600102
Keywords
NMR spectroscopy; prolyl oligopeptidase; protein dynamics; protein-protein interactions; SAXS
Funding
- Institute for Research in Biomedicine, MINECO-FEDER [Bio2013-40716-R, CTQ2013-48287, CTQ2012-32183/BQU]
- Generalitat de Catalunya (XRB)
- Generalitat de Catalunya (Grup Consolidat) [2014SGR521]
- Instituto de Salud Carlos III
- Agence Nationale de la Recherche [SPIN-HD-ANR-CHEX-2011]
- ATIP-Avenir program
- INSERM
- University of Copenhagen
- ICREA Funding Source: Custom
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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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