6luq
From Proteopedia
(Difference between revisions)
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<StructureSection load='6luq' size='340' side='right'caption='[[6luq]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='6luq' size='340' side='right'caption='[[6luq]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6luq]] is a 1 chain structure. 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 [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> |
</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='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> | ||
| + | <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='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='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'>[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> | <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> | ||
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== Function == | == 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> | [[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> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == 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. | ||
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| + | 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<ref>PMID:32103023</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6luq" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Lysozyme]] | [[Category: Lysozyme]] | ||
Revision as of 07:54, 11 March 2020
Haloperidol bound D2 dopamine receptor structure inspired discovery of subtype selective ligands
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Categories: Human | Large Structures | Lysozyme | Chen, Z | Cheng, J | Fan, L | Luo, Z | Nie, F | Qi, J | Tan, L | Wang, S | D2 dopamine receptor | Dopamine receptor | Gpcr | Haloperidol | Membrane protein
