5zhp

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'''Unreleased structure'''
 
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The entry 5zhp is ON HOLD until Paper Publication
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==M3 muscarinic acetylcholine receptor in complex with a selective antagonist==
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<StructureSection load='5zhp' size='340' side='right' caption='[[5zhp]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[5zhp]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5ZHP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ZHP FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9EC:(1R,2R,4S,5S,7s)-7-({[4-fluoro-2-(thiophen-2-yl)phenyl]carbamoyl}oxy)-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.0~2,4~]nonan-9-ium'>9EC</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=MAL:MALTOSE'>MAL</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG4:TETRAETHYLENE+GLYCOL'>PG4</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Chrm3, Chrm-3 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
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<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=5zhp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5zhp OCA], [http://pdbe.org/5zhp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5zhp RCSB], [http://www.ebi.ac.uk/pdbsum/5zhp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5zhp ProSAT]</span></td></tr>
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</table>
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== Function ==
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[[http://www.uniprot.org/uniprot/ACM3_RAT ACM3_RAT]] The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.<ref>PMID:1527051</ref> <ref>PMID:1657592</ref> <ref>PMID:22358844</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Drugs that treat chronic obstructive pulmonary disease by antagonizing the M3 muscarinic acetylcholine receptor (M3R) have had a significant effect on health, but can suffer from their lack of selectivity against the M2R subtype, which modulates heart rate. Beginning with the crystal structures of M2R and M3R, we exploited a single amino acid difference in their orthosteric binding pockets using molecular docking and structure-based design. The resulting M3R antagonists had up to 100-fold selectivity over M2R in affinity and over 1,000-fold selectivity in vivo. The crystal structure of the M3R-selective antagonist in complex with M3R corresponded closely to the docking-predicted geometry, providing a template for further optimization.
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Authors:
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Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists.,Liu H, Hofmann J, Fish I, Schaake B, Eitel K, Bartuschat A, Kaindl J, Rampp H, Banerjee A, Hubner H, Clark MJ, Vincent SG, Fisher JT, Heinrich MR, Hirata K, Liu X, Sunahara RK, Shoichet BK, Kobilka BK, Gmeiner P Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):12046-12050. doi:, 10.1073/pnas.1813988115. Epub 2018 Nov 7. PMID:30404914<ref>PMID:30404914</ref>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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<div class="pdbe-citations 5zhp" style="background-color:#fffaf0;"></div>
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Buffalo rat]]
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[[Category: Banerjee, A]]
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[[Category: Bartuschat, A]]
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[[Category: Clark, M J]]
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[[Category: Eitel, K]]
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[[Category: Fish, I]]
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[[Category: Fisher, J]]
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[[Category: Gmeiner, P]]
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[[Category: Heinrich, M]]
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[[Category: Hirata, K]]
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[[Category: Hofmann, J]]
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[[Category: Hubner, H]]
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[[Category: Kaindl, J]]
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[[Category: Kobilka, B K]]
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[[Category: Liu, H]]
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[[Category: Liu, X]]
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[[Category: Rampp, H]]
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[[Category: Schaake, B]]
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[[Category: Shoichet, B K]]
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[[Category: Sunahara, R K]]
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[[Category: Vincent, S G]]
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[[Category: G protein coupled receptor]]
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[[Category: Membrane protein]]

Revision as of 20:23, 2 December 2018

M3 muscarinic acetylcholine receptor in complex with a selective antagonist

5zhp, resolution 3.10Å

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