6b73
From Proteopedia
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<StructureSection load='6b73' size='340' side='right' caption='[[6b73]], [[Resolution|resolution]] 3.10Å' scene=''> | <StructureSection load='6b73' size='340' side='right' caption='[[6b73]], [[Resolution|resolution]] 3.10Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[6b73]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B73 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6b73]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_coli"_migula_1895 "bacillus coli" migula 1895] and [http://en.wikipedia.org/wiki/Camelus_glama Camelus glama]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6B73 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6B73 FirstGlance]. <br> |
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=CVV:N-[(5alpha,6beta)-17-(cyclopropylmethyl)-3-hydroxy-7,8-didehydro-4,5-epoxymorphinan-6-yl]-3-iodobenzamide'>CVV</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=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=CVV:N-[(5alpha,6beta)-17-(cyclopropylmethyl)-3-hydroxy-7,8-didehydro-4,5-epoxymorphinan-6-yl]-3-iodobenzamide'>CVV</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">OPRK1, OPRK ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=562 "Bacillus coli" Migula 1895])</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=6b73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b73 OCA], [http://pdbe.org/6b73 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b73 RCSB], [http://www.ebi.ac.uk/pdbsum/6b73 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b73 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=6b73 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6b73 OCA], [http://pdbe.org/6b73 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6b73 RCSB], [http://www.ebi.ac.uk/pdbsum/6b73 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6b73 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function. | [[http://www.uniprot.org/uniprot/C562_ECOLX C562_ECOLX]] Electron-transport protein of unknown function. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The kappa-opioid receptor (KOP) mediates the actions of opioids with hallucinogenic, dysphoric, and analgesic activities. The design of KOP analgesics devoid of hallucinatory and dysphoric effects has been hindered by an incomplete structural and mechanistic understanding of KOP agonist actions. Here, we provide a crystal structure of human KOP in complex with the potent epoxymorphinan opioid agonist MP1104 and an active-state-stabilizing nanobody. Comparisons between inactive- and active-state opioid receptor structures reveal substantial conformational changes in the binding pocket and intracellular and extracellular regions. Extensive structural analysis and experimental validation illuminate key residues that propagate larger-scale structural rearrangements and transducer binding that, collectively, elucidate the structural determinants of KOP pharmacology, function, and biased signaling. These molecular insights promise to accelerate the structure-guided design of safer and more effective kappa-opioid receptor therapeutics. | ||
| + | |||
| + | Structure of the Nanobody-Stabilized Active State of the Kappa Opioid Receptor.,Che T, Majumdar S, Zaidi SA, Ondachi P, McCorvy JD, Wang S, Mosier PD, Uprety R, Vardy E, Krumm BE, Han GW, Lee MY, Pardon E, Steyaert J, Huang XP, Strachan RT, Tribo AR, Pasternak GW, Carroll FI, Stevens RC, Cherezov V, Katritch V, Wacker D, Roth BL Cell. 2018 Jan 11;172(1-2):55-67.e15. doi: 10.1016/j.cell.2017.12.011. Epub 2018 , Jan 4. PMID:29307491<ref>PMID:29307491</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6b73" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Bacillus coli migula 1895]] | ||
| + | [[Category: Camelus glama]] | ||
[[Category: Carroll, I F]] | [[Category: Carroll, I F]] | ||
[[Category: Che, T]] | [[Category: Che, T]] | ||
Revision as of 20:54, 24 January 2018
Crystal Structure of a nanobody-stabilized active state of the kappa-opioid receptor
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Categories: Bacillus coli migula 1895 | Camelus glama | Carroll, I F | Che, T | Cherezov, V | Han, G W | Huang, X P | Katritch, V | Kormos, C | Krumm, B E | Lee, M Y | Majumdar, S | McCorvy, J D | Mosier, P D | Pardon, E | Pasternak, G W | Roth, B L | Stevens, R C | Steyaert, J | Strachan, R T | Tribo, A R | Uprety, R | Vardy, E | Wacker, D | Wang, S | Zaidi, S A | Active state | Addiction | Gpcr | Lcp | Membrane protein | Membrane protein-agonist complex | Morphinan | Nanobody | Opioid receptor | Structure-function
