View source for 5dsg


==Structure of the M4 muscarinic acetylcholine receptor (M4-mT4L) bound to tiotropium==
<StructureSection load='5dsg' size='340' side='right'caption='[[5dsg]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5dsg]] is a 2 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=5DSG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5DSG 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]] 2.6&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=0HK:(1R,2R,4S,5S,7S)-7-{[HYDROXY(DITHIOPHEN-2-YL)ACETYL]OXY}-9,9-DIMETHYL-3-OXA-9-AZONIATRICYCLO[3.3.1.0~2,4~]NONANE'>0HK</scene>, <scene name='pdbligand=EDT:{[-(BIS-CARBOXYMETHYL-AMINO)-ETHYL]-CARBOXYMETHYL-AMINO}-ACETIC+ACID'>EDT</scene>, <scene name='pdbligand=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P6G:HEXAETHYLENE+GLYCOL'>P6G</scene>, <scene name='pdbligand=PG6:1-(2-METHOXY-ETHOXY)-2-{2-[2-(2-METHOXY-ETHOXY]-ETHOXY}-ETHANE'>PG6</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=5dsg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5dsg OCA], [https://pdbe.org/5dsg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5dsg RCSB], [https://www.ebi.ac.uk/pdbsum/5dsg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5dsg ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ACM4_HUMAN ACM4_HUMAN] 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 inhibition of adenylate cyclase.[https://www.uniprot.org/uniprot/ENLYS_BPT4 ENLYS_BPT4] Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.<ref>PMID:22389108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Muscarinic M1-M5 acetylcholine receptors are G-protein-coupled receptors that regulate many vital functions of the central and peripheral nervous systems. In particular, the M1 and M4 receptor subtypes have emerged as attractive drug targets for treatments of neurological disorders, such as Alzheimer's disease and schizophrenia, but the high conservation of the acetylcholine-binding pocket has spurred current research into targeting allosteric sites on these receptors. Here we report the crystal structures of the M1 and M4 muscarinic receptors bound to the inverse agonist, tiotropium. Comparison of these structures with each other, as well as with the previously reported M2 and M3 receptor structures, reveals differences in the orthosteric and allosteric binding sites that contribute to a role in drug selectivity at this important receptor family. We also report identification of a cluster of residues that form a network linking the orthosteric and allosteric sites of the M4 receptor, which provides new insight into how allosteric modulation may be transmitted between the two spatially distinct domains.

Crystal structures of the M1 and M4 muscarinic acetylcholine receptors.,Thal DM, Sun B, Feng D, Nawaratne V, Leach K, Felder CC, Bures MG, Evans DA, Weis WI, Bachhawat P, Kobilka TS, Sexton PM, Kobilka BK, Christopoulos A Nature. 2016 Mar 17;531(7594):335-40. doi: 10.1038/nature17188. Epub 2016 Mar 9. PMID:26958838<ref>PMID:26958838</ref>

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

==See Also==
*[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia virus T4]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Christopoulos A]]
[[Category: Kobilka BK]]
[[Category: Sexton PM]]
[[Category: Thal DM]]