View source for 5wiu


==Structure of the human D4 Dopamine receptor in complex with Nemonapride==
<StructureSection load='5wiu' size='340' side='right'caption='[[5wiu]], [[Resolution|resolution]] 1.96&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5wiu]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5WIU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5WIU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.962&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AQD:5-chloranyl-2-methoxy-4-(methylamino)-~{N}-[(2~{R},3~{R})-2-methyl-1-(phenylmethyl)pyrrolidin-3-yl]benzamide'>AQD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5wiu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5wiu OCA], [https://pdbe.org/5wiu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5wiu RCSB], [https://www.ebi.ac.uk/pdbsum/5wiu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5wiu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/DRD4_HUMAN 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).[https://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX] Electron-transport protein of unknown function.
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== 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<ref>PMID:29051383</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 5wiu" style="background-color:#fffaf0;"></div>

==See Also==
*[[Dopamine receptor 3D structures|Dopamine receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Betz RM]]
[[Category: Che T]]
[[Category: Dror RO]]
[[Category: Huang X-P]]
[[Category: Levit A]]
[[Category: McCorvy JD]]
[[Category: Roth BL]]
[[Category: Shoichet BK]]
[[Category: Venkatakrishnan AJ]]
[[Category: Wacker D]]
[[Category: Wang S]]