Active-Site-Directed Inhibitors of Prolyl Oligopeptidase Abolish Its Conformational Dynamics.
Chembiochem
; 17(10): 913-7, 2016 05 17.
Article
em En
| MEDLINE
| ID: mdl-26918396
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.
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MEDLINE
Assunto principal:
Serina Endopeptidases
/
Inibidores Enzimáticos
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article