Three-dimensional model of the human urotensin-II receptor: Docking of human urotensin-II and nonpeptide antagonists in the binding site and comparison with an antagonist pharmacophore model
| Autor: | Nathalie Colloc'h, Jana Sopkova-de Oliveira Santos, Isabelle Milazzo-Segalas, Sylvain Rault, Ronan Bureau, Jordi Rodrigo, Elodie Lescot |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Rhodopsin Molecular model Protein Conformation Stereochemistry Urotensins Molecular Sequence Data Urotensin-II receptor Biology Ligands Biochemistry Piperazines Receptors G-Protein-Coupled chemistry.chemical_compound Structural Biology Animals Humans Urea Amino Acid Sequence Homology modeling Receptor Molecular Biology G protein-coupled receptor Binding Sites Benzazepines chemistry Docking (molecular) Drug Design Aminoquinolines Pharmacophore Urotensin-II Sequence Alignment |
| Zdroj: | Proteins: Structure, Function, and Bioinformatics. 73:173-184 |
| ISSN: | 0887-3585 |
| DOI: | 10.1002/prot.22050 |
| Popis: | Human urotensin-II (hU-II) is a cyclic peptide that plays a central role in cardiovascular homeostasis and is considered to be the most potent mammalian vasoconstrictor identified to date. It is a natural ligand of the human urotensin-II (hUT-II) receptor, a member of the family of rhodopsin-like G-protein-coupled receptors. To understand the molecular interactions of hU-II and certain antagonists with the hUT-II receptor, a model of the hUT-II receptor in an active conformation with all its connecting loops was constructed by homology modeling. The initial model was placed in a pre-equilibrated lipid bilayer and re-equilibrated by several procedures of energy minimization and molecular dynamics simulations. Docking studies were performed for hU-II and for a series of nonpeptide hUT-II receptor antagonists in the active site of the modeled receptor structure. Results of the hU-II docking study are in agreement with our previous work and with experimental data showing the contribution of the extracellular loops II and III to ligand recognition. The docking of hU-II nonpeptide antagonists allows identification of key molecular interactions and confirms a previously reported hU-II antagonist pharmacophore model. The results of the present studies will be used in structure-based drug design for developing novel antagonists for the hUT-II receptor. Proteins 2008. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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