Structural Basis for Agonism and Antagonism for a Set of Chemically Related Progesterone Receptor Modulators
| Autor: | Ross McGuire, Rolien Bosch, Jacob de Vlieg, Niall M. Hamilton, Olaf Nimz, Koen J. Dechering, Angus R. Brown, Scott J. Lusher, Tsang Wai Lam, Arthur Oubrie, Diep Vu-Pham, Hans C.A. Raaijmakers |
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| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Agonist Protein Conformation medicine.drug_class Stereochemistry Drug Evaluation Preclinical Molecular Conformation CHO Cells Plasma protein binding Crystallography X-Ray Ligands Biochemistry Cricetulus Cricetinae Progesterone receptor medicine Animals Binding site Receptor GeneralLiterature_REFERENCE(e.g. dictionaries encyclopedias glossaries) Molecular Biology Progesterone Binding Sites Chemistry Cell Biology Mifepristone Nuclear receptor Drug Design Protein Structure and Folding Research Programm of Institute for Molecules and Materials Biophysical Chemistry Norethindrone Receptors Progesterone Antagonism Dimerization Protein Binding medicine.drug |
| Zdroj: | Journal of Biological Chemistry, 286, 35079-35086 Journal of Biological Chemistry, 286, 40, pp. 35079-35086 |
| ISSN: | 0021-9258 |
| Popis: | The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes. |
| Databáze: | OpenAIRE |
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