6ol9: Difference between revisions
No edit summary |
No edit summary |
||
| Line 3: | Line 3: | ||
<StructureSection load='6ol9' size='340' side='right'caption='[[6ol9]], [[Resolution|resolution]] 2.54Å' scene=''> | <StructureSection load='6ol9' size='340' side='right'caption='[[6ol9]], [[Resolution|resolution]] 2.54Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6ol9]] is a 1 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6ol9]] 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=6OL9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6OL9 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.541Å</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=OLA:OLEIC+ACID'>OLA</scene>, <scene name='pdbligand=OLC:(2R)-2,3-DIHYDROXYPROPYL+(9Z)-OCTADEC-9-ENOATE'>OLC</scene>, <scene name='pdbligand=P33:3,6,9,12,15,18-HEXAOXAICOSANE-1,20-DIOL'>P33</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=6ol9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6ol9 OCA], [https://pdbe.org/6ol9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6ol9 RCSB], [https://www.ebi.ac.uk/pdbsum/6ol9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6ol9 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[[ | [https://www.uniprot.org/uniprot/D9IEF7_BPT4 D9IEF7_BPT4] [https://www.uniprot.org/uniprot/ACM5_HUMAN ACM5_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 Pi turnover. | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 20: | Line 19: | ||
</div> | </div> | ||
<div class="pdbe-citations 6ol9" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6ol9" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Lysozyme 3D structures|Lysozyme 3D structures]] | |||
*[[Muscarinic acetylcholine receptor|Muscarinic acetylcholine receptor]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Escherichia virus T4]] | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Christopoulos A]] | |||
[[Category: Christopoulos | [[Category: Thal DM]] | ||
[[Category: Thal | [[Category: Vuckovic Z]] | ||
[[Category: Vuckovic | |||
Latest revision as of 10:12, 11 October 2023
Structure of the M5 muscarinic acetylcholine receptor (M5-T4L) bound to tiotropiumStructure of the M5 muscarinic acetylcholine receptor (M5-T4L) bound to tiotropium
Structural highlights
FunctionD9IEF7_BPT4 ACM5_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 Pi turnover. Publication Abstract from PubMedThe human M5 muscarinic acetylcholine receptor (mAChR) has recently emerged as an exciting therapeutic target for treating a range of disorders, including drug addiction. However, a lack of structural information for this receptor subtype has limited further drug development and validation. Here we report a high-resolution crystal structure of the human M5 mAChR bound to the clinically used inverse agonist, tiotropium. This structure allowed for a comparison across all 5 mAChR family members that revealed important differences in both orthosteric and allosteric sites that could inform the rational design of selective ligands. These structural studies, together with chimeric swaps between the extracellular regions of the M2 and M5 mAChRs, provided structural insight into kinetic selectivity, where ligands show differential residency times between related family members. Collectively, our study provides important insights into the nature of orthosteric and allosteric ligand interaction across the mAChR family that could be exploited for the design of selective drugs. Crystal structure of the M5 muscarinic acetylcholine receptor.,Vuckovic Z, Gentry PR, Berizzi AE, Hirata K, Varghese S, Thompson G, van der Westhuizen ET, Burger WAC, Rahmani R, Valant C, Langmead CJ, Lindsley CW, Baell JB, Tobin AB, Sexton PM, Christopoulos A, Thal DM Proc Natl Acad Sci U S A. 2019 Nov 26. pii: 1914446116. doi:, 10.1073/pnas.1914446116. PMID:31772027[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
|
| ||||||||||||||||||