6IQL
Crystal structure of dopamine receptor D4 bound to the subtype-selective ligand, L745870
Summary for 6IQL
| Entry DOI | 10.2210/pdb6iql/pdb |
| Descriptor | D(4) dopamine receptor,Soluble cytochrome b562,D(4) dopamine receptor, 3-{[4-(4-chlorophenyl)piperazin-1-yl]methyl}-1H-pyrrolo[2,3-b]pyridine (2 entities in total) |
| Functional Keywords | gpcr, drd4, l745870, ligand, dimerization, signaling protein |
| Biological source | Mus musculus (Mouse) More |
| Total number of polymer chains | 2 |
| Total formula weight | 87785.01 |
| Authors | Zhou, Y.,Cao, C.,Zhang, X.C. (deposition date: 2018-11-08, release date: 2019-12-04, Last modification date: 2024-11-13) |
| Primary citation | Zhou, Y.,Cao, C.,He, L.,Wang, X.,Zhang, X.C. Crystal structure of dopamine receptor D4 bound to the subtype selective ligand, L745870. Elife, 8:-, 2019 Cited by PubMed Abstract: Multiple subtypes of dopamine receptors within the GPCR superfamily regulate neurological processes through various downstream signaling pathways. A crucial question about the dopamine receptor family is what structural features determine the subtype-selectivity of potential drugs. Here, we report the 3.5-angstrom crystal structure of mouse dopamine receptor D4 (DRD4) complexed with a subtype-selective antagonist, L745870. Our structure reveals a secondary binding pocket extended from the orthosteric ligand-binding pocket to a DRD4-specific crevice located between transmembrane helices 2 and 3. Additional mutagenesis studies suggest that the antagonist L745870 prevents DRD4 activation by blocking the relative movement between transmembrane helices 2 and 3. These results expand our knowledge of the molecular basis for the physiological functions of DRD4 and assist new drug design. PubMed: 31750832DOI: 10.7554/eLife.48822 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.5 Å) |
Structure validation
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