5WIV

Structure of the sodium-bound human D4 Dopamine receptor in complex with Nemonapride

Summary for 5WIV

• Entry DOI: 10.2210/pdb5wiv/pdb
• Related: 5WIU
• Descriptor: D(4) dopamine receptor, soluble cytochrome b562 chimera, Nemonapride, PHOSPHATE ION, ... (7 entities in total)
• Functional Keywords: gpcr, dopamine receptor, antagonist, sodium, signaling protein-antagonist complex, signaling protein/antagonist
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 1
• Total formula weight: 49407.12

Authors

Wacker, D.,Wang, S.,Levit, A.,Che, T.,Betz, R.M.,McCorvy, J.D.,Venkatakrishnan, A.J.,Huang, X.-P.,Dror, R.O.,Shoichet, B.K.,Roth, B.L. (deposition date: 2017-07-20, release date: 2017-10-18, Last modification date: 2024-10-30)

Primary citation

Wang, S.,Wacker, D.,Levit, A.,Che, T.,Betz, R.M.,McCorvy, J.D.,Venkatakrishnan, A.J.,Huang, X.P.,Dror, R.O.,Shoichet, B.K.,Roth, B.L.
D4 dopamine receptor high-resolution structures enable the discovery of selective agonists.
Science, 358:381-386, 2017

PubMed Abstract: Dopamine receptors are implicated in the pathogenesis and treatment of nearly every neuropsychiatric disorder. Although thousands of drugs interact with these receptors, our molecular understanding of dopaminergic drug selectivity and design remains clouded. To illuminate dopamine receptor structure, function, and ligand recognition, we determined crystal structures of the D dopamine receptor in its inactive state bound to the antipsychotic drug nemonapride, with resolutions up to 1.95 angstroms. These structures suggest a mechanism for the control of constitutive signaling, and their unusually high resolution enabled a structure-based campaign for new agonists of the D dopamine receptor. The ability to efficiently exploit structure for specific probe discovery-rapidly moving from elucidating receptor structure to discovering previously unrecognized, selective agonists-testifies to the power of structure-based approaches.

PubMed: 29051383
DOI: 10.1126/science.aan5468

Experimental method

X-RAY DIFFRACTION (2.143 Å)