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6luq

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Current revision

Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands

Structural highlights

6luq is a 1 chain structure with sequence from Escherichia virus T4 and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.1Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

DRD2_HUMAN Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258).

Function

D9IEF7_BPT4 DRD2_HUMAN Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).^[1] ^[2]

Publication Abstract from PubMed

The D2 dopamine receptor (DRD2) is one of the most well-established therapeutic targets for neuropsychiatric and endocrine disorders. Most clinically approved and investigational drugs that target this receptor are known to be subfamily-selective for all three D2-like receptors, rather than subtype-selective for only DRD2. Here, we report the crystal structure of DRD2 bound to the most commonly used antipsychotic drug, haloperidol. The structures suggest an extended binding pocket for DRD2 that distinguishes it from other D2-like subtypes. A detailed analysis of the structures illuminates key structural determinants essential for DRD2 activation and subtype selectivity. A structure-based and mechanism-driven screening combined with a lead optimization approach yield DRD2 highly selective agonists, which could be used as chemical probes for studying the physiological and pathological functions of DRD2 as well as promising therapeutic leads devoid of promiscuity.

Haloperidol bound D2 dopamine receptor structure inspired the discovery of subtype selective ligands.,Fan L, Tan L, Chen Z, Qi J, Nie F, Luo Z, Cheng J, Wang S Nat Commun. 2020 Feb 26;11(1):1074. doi: 10.1038/s41467-020-14884-y. PMID:32103023^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Albizu L, Holloway T, Gonzalez-Maeso J, Sealfon SC. Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology. 2011 Sep;61(4):770-7. doi: 10.1016/j.neuropharm.2011.05.023., Epub 2011 May 27. PMID:21645528 doi:http://dx.doi.org/10.1016/j.neuropharm.2011.05.023
↑ Johnston CA, Siderovski DP. Structural basis for nucleotide exchange on G alpha i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):2001-6. Epub 2007 Jan 30. PMID:17264214
↑ Fan L, Tan L, Chen Z, Qi J, Nie F, Luo Z, Cheng J, Wang S. Haloperidol bound D2 dopamine receptor structure inspired the discovery of subtype selective ligands. Nat Commun. 2020 Feb 26;11(1):1074. doi: 10.1038/s41467-020-14884-y. PMID:32103023 doi:http://dx.doi.org/10.1038/s41467-020-14884-y

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6luq"

@@ Line 3: / Line 3: @@
 <StructureSection load='6luq' size='340' side='right'caption='[[6luq]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6luq]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6LUQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6LUQ FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6luq]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_virus_T4 Escherichia virus T4] 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=6LUQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6LUQ FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GMJ:4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one'>GMJ</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.1&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DRD2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GMJ:4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one'>GMJ</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene></td></tr>
-<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Lysozyme Lysozyme], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.2.1.17 3.2.1.17] </span></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=6luq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6luq OCA], [https://pdbe.org/6luq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6luq RCSB], [https://www.ebi.ac.uk/pdbsum/6luq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6luq ProSAT]</span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6luq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6luq OCA], [http://pdbe.org/6luq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6luq RCSB], [http://www.ebi.ac.uk/pdbsum/6luq PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6luq ProSAT]</span></td></tr>
 </table>
 == Disease ==
-[[http://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN]] Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258).
+[https://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN] Myoclonic dystonia 11. The gene represented in this entry may be involved in disease pathogenesis. DRD2 mutations in myoclonic dystonia patients are rare, and their contribution to disease phenotype is unclear (PubMed:10716258).
 == Function ==
-[[http://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN]] Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).<ref>PMID:21645528</ref> <ref>PMID:17264214</ref>
+[https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/DRD2_HUMAN DRD2_HUMAN] Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase (By similarity).<ref>PMID:21645528</ref> <ref>PMID:17264214</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 22: / Line 21: @@
 </div>
 <div class="pdbe-citations 6luq" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Dopamine receptor 3D structures|Dopamine receptor 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Escherichia virus T4]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lysozyme]]
+[[Category: Chen Z]]
-[[Category: Chen, Z]]
+[[Category: Cheng J]]
-[[Category: Cheng, J]]
+[[Category: Fan L]]
-[[Category: Fan, L]]
+[[Category: Luo Z]]
-[[Category: Luo, Z]]
+[[Category: Nie F]]
-[[Category: Nie, F]]
+[[Category: Qi J]]
-[[Category: Qi, J]]
+[[Category: Tan L]]
-[[Category: Tan, L]]
+[[Category: Wang S]]
-[[Category: Wang, S]]
-[[Category: D2 dopamine receptor]]
-[[Category: Dopamine receptor]]
-[[Category: Gpcr]]
-[[Category: Haloperidol]]
-[[Category: Membrane protein]]

6luq

From Proteopedia

Current revision

Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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