9M4T
CryoEM structure of the alpha1AAR complex with silodosin
This is a non-PDB format compatible entry.
Summary for 9M4T
| Entry DOI | 10.2210/pdb9m4t/pdb |
| EMDB information | 63629 |
| Descriptor | Alpha-1A adrenergic receptor, Silodosin (2 entities in total) |
| Functional Keywords | gpcr, alpha1aar, silodosin, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 1 |
| Total formula weight | 36288.03 |
| Authors | Liu, S.S.,Guo, Q.,Wang, D.D.,Tao, Y.Y.,Jiao, H.Z. (deposition date: 2025-03-04, release date: 2025-07-02) |
| Primary citation | Liu, S.,Jiao, H.,Tao, Y.,Wang, D.,Guo, Q. Molecular mechanism of antagonist recognition and regulation of the alpha1A-adrenoceptor J.Biol.Chem., :110348-110348, 2025 Cited by PubMed Abstract: The α-adrenoceptor (αAR) is a critically important class of G protein-coupled receptors (GPCRs), comprising three subtypes: αAR, αAR, and αAR. Currently, drugs targeting αAR have been used in the treatment of various diseases. Notably, antagonists of αAR play a pivotal role in the management of benign prostatic hyperplasia (BPH). In recent years, researchers have developed selective antagonists for the αAR subtype that have a minimal impact on blood pressure for the treatment of BPH. However, these agents still exhibit certain side effects, necessitating the continuous development of new medications to mitigate adverse reactions while achieving more precise regulation. We report the cryo-EM structures of the αAR selective antagonist doxazosin and the αAR subtype selective antagonist silodosin in complex with αAR, demonstrating that M292 and V185 are key residues that confer subtype selectivity to silodosin. Additionally, modifications to αAR enhanced silodosin's inhibitory efficacy against αAR. These findings deepen our understanding of the recognition patterns of αAR antagonists, revealing the molecular principles underlying the selective binding of silodosin to αAR and promoting further research and development of subtype selective drugs targeting αAR. PubMed: 40484377DOI: 10.1016/j.jbc.2025.110348 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.19 Å) |
Structure validation
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