Active-Site-Directed Inhibitors of Prolyl Oligopeptidase Abolish Its Conformational Dynamics
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 (PPI...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | Universitat Politècnica de Catalunya (UPC) |
| Repositorio: | UPCommons. Portal del coneixement obert de la UPC |
| Idioma: | inglés |
| OAI Identifier: | oai:upcommons.upc.edu:2117/100311 |
| Acceso en línea: | https://hdl.handle.net/2117/100311 https://dx.doi.org/10.1002/cbic.201600102 |
| Access Level: | acceso abierto |
| Palabra clave: | Proteins--Analysis Protein–protein interactions (PPIs) Prolyl oligopeptidase (POP) Proteïnes--Anàlisi Àrees temàtiques de la UPC::Enginyeria biomèdica |
| Sumario: | 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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