Structural highlights
Function
[DRD4_HUMAN] Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Publication Abstract from PubMed
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 D4 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 D4 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.
D4 dopamine receptor high-resolution structures enable the discovery of selective agonists.,Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL Science. 2017 Oct 20;358(6361):381-386. doi: 10.1126/science.aan5468. PMID:29051383[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wang S, Wacker D, Levit A, Che T, Betz RM, McCorvy JD, Venkatakrishnan AJ, Huang XP, Dror RO, Shoichet BK, Roth BL. D4 dopamine receptor high-resolution structures enable the discovery of selective agonists. Science. 2017 Oct 20;358(6361):381-386. doi: 10.1126/science.aan5468. PMID:29051383 doi:http://dx.doi.org/10.1126/science.aan5468
