Predicted 3D structure for the human beta 2 adrenergic receptor and its binding site for agonists and antagonists
| Autor: | Victor Wai Tak Kam, Spencer E. Hall, Nagarajan Vaidehi, Wely B. Floriano, William A. Goddard, Peter L. Freddolino, Rene J. Trabanino, M. Yashar S. Kalani |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Models
Molecular Multidisciplinary Binding Sites Epinephrine Chemistry Stereochemistry Protein Conformation Mutagenesis Adrenergic beta-Antagonists Cell Membrane Adrenergic Adrenergic beta-Agonists Biological Sciences Ligands β2 adrenergic receptor Norepinephrine Protein structure Humans Receptors Adrenergic beta-2 Binding site Receptor Binding affinities |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 101(9) |
| ISSN: | 0027-8424 |
| Popis: | We report the 3D structure of human β2 adrenergic receptor (AR) predicted by using the MembStruk first principles method. To validate this structure, we use the HierDock first principles method to predict the ligand-binding sites for epinephrine and norepinephrine and for eight other ligands, including agonists and antagonists to β2 AR and ligands not observed to bind to β2 AR. The binding sites agree well with available mutagenesis data, and the calculated relative binding energies correlate reasonably with measured binding affinities. In addition, we find characteristic differences in the predicted binding sites of known agonists and antagonists that allow us to infer the likely activity of other ligands. The predicted ligand-binding properties validate the methods used to predict the 3D structure and function. This validation is a successful step toward applying these procedures to predict the 3D structures and function of the other eight subtypes of ARs, which should enable the development of subtype-specific antagonists and agonists with reduced side effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|