A Three-Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors
Saleh N, Saladino G, Gervasio FL, Haensele E, Banting L, Whitley DC, Santos JSDO, Bureau R, Clark T (2016)
Publication Status: Published
Publication Type: Journal article
Publication year: 2016
Journal
Publisher: WILEY-V C H VERLAG GMBH
Book Volume: 55
Pages Range: 8008-8012
Journal Issue: 28
Abstract
Molecular-dynamics simulations with metadynamics enhanced sampling reveal three distinct binding sites for arginine vasopressin (AVP) within its V-2-receptor (V2R). Two of these, the vestibule and intermediate sites, block (antagonize) the receptor, and the third is the orthosteric activation (agonist) site. The contacts found for the orthosteric site satisfy all the requirements deduced from mutagenesis experiments. Metadynamics simulations for V2R and its V1aR-analog give an excellent correlation with experimental binding free energies by assuming that the most stable binding site in the simulations corresponds to the experimental binding free energy in each case. The resulting three-site mechanism separates agonists from antagonists and explains subtype selectivity.
Authors with CRIS profile
Involved external institutions
Université de Caen Basse-Normandie
France (FR)
University of Portsmouth
United Kingdom (GB)
University College London (UCL)
United Kingdom (GB)
France (FR)
University of Portsmouth
United Kingdom (GB)
University College London (UCL)
United Kingdom (GB)
How to cite
APA:
Saleh, N., Saladino, G., Gervasio, F.L., Haensele, E., Banting, L., Whitley, D.C.,... Clark, T. (2016). A Three-Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors. Angewandte Chemie International Edition, 55(28), 8008-8012. https://dx.doi.org/10.1002/anie.201602729
MLA:
Saleh, Noureldin, et al. "A Three-Site Mechanism for Agonist/Antagonist Selective Binding to Vasopressin Receptors." Angewandte Chemie International Edition 55.28 (2016): 8008-8012.
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