12iy: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 12iy is ~~ON HOLD until Paper~~ Publication

==Locally refined cryo-EM structure of human cannabinoid receptor 2 with agonist '5249==

== Structural highlights ==

<table><tr><td colspan='2'>[[12iy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=12IY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=12IY FirstGlance]. <br>

</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.94Å</td></tr>

<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DB5:(3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]ethyl}-2-benzofuran-1(3H)-one'>A1DB5</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=12iy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=12iy OCA], [https://pdbe.org/12iy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=12iy RCSB], [https://www.ebi.ac.uk/pdbsum/12iy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=12iy ProSAT]</span></td></tr>

</table>

== Function ==

[https://www.uniprot.org/uniprot/CNR2_HUMAN CNR2_HUMAN] Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.<ref>PMID:10051546</ref> <ref>PMID:12663043</ref> <ref>PMID:12711605</ref> <ref>PMID:18692962</ref>

== Publication Abstract from PubMed ==

Cannabinoid receptors are both therapeutically attractive and are interesting model systems for structure-based methods. Here we investigated topical questions in library docking using the CB2 receptor. While a CB1R docking campaign found potent but nonselective ligands, here subtype selective ligands were found by targeting polar residues. Hit rates and hit affinities improved with library size, but docking against active and inactive receptor states did not reliably bias toward agonists or antagonists. Cryo-EM structures of two of the new agonists superposed well on the docking predictions. Structure-based optimization led to 10- to 140-fold improvements within three series, consistent with well-behaved ligands. Hit rates with an explicit 2.6 billion molecule library resembled those of an implied 11 billion molecule library from a building-block method, supporting the latter's ability to explore this space, though higher affinities were discovered from the explicit set. Implications for future studies are considered.

~~Authors:~~ Sacco, M., Wu, C., ~~Singal~~, B., Skiniotis, G.

Library Docking for Cannabinoid-2 Receptor Ligands.,Rachman MM, Iliopoulos-Tsoutsouvas C, Sacco MD, Xu X, Wu CG, Santos E, Glenn IS, Paris L, Cahill MK, Ganapathy S, Tummino TA, Moroz YS, Radchenko DS, Okorie M, Tawfik VL, Irwin JJ, Makriyannis A, Skiniotis G, Shoichet BK J Med Chem. 2026 Jul 3. doi: 10.1021/acs.jmedchem.6c00835. PMID:42397716<ref>PMID:42397716</ref>

~~Description~~: ~~Locally refined cryo-EM structure of human cannabinoid receptor 2 with agonist ''5249~~

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>

[[Category: ~~Unreleased Structures~~]]

</div>

[[Category: ~~Singal, B~~]]

[[Category: Sacco, M]]

== References ==

[[Category: ~~Wu, C~~]]

[[Category: Skiniotis, G]]

__TOC__

</StructureSection>

[[Category: Homo sapiens]]

[[Category: Large Structures]]

[[Category: Sacco M]]

[[Category: Singal B]]

[[Category: Skiniotis G]]

[[Category: Wu C]]

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@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 12iy is ON HOLD  until Paper Publication
+==Locally refined cryo-EM structure of human cannabinoid receptor 2 with agonist '5249==
+<StructureSection load='12iy' size='340' side='right'caption='[[12iy]], [[Resolution|resolution]] 2.94&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[12iy]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=12IY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=12IY FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 2.94&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DB5:(3R)-3-{2-oxo-2-[7-(trifluoromethyl)-3,4-dihydro-1,5-benzoxazepin-5(2H)-yl]ethyl}-2-benzofuran-1(3H)-one'>A1DB5</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=12iy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=12iy OCA], [https://pdbe.org/12iy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=12iy RCSB], [https://www.ebi.ac.uk/pdbsum/12iy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=12iy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/CNR2_HUMAN CNR2_HUMAN] Heterotrimeric G protein-coupled receptor for endocannabinoid 2-arachidonoylglycerol mediating inhibition of adenylate cyclase. May function in inflammatory response, nociceptive transmission and bone homeostasis.<ref>PMID:10051546</ref> <ref>PMID:12663043</ref> <ref>PMID:12711605</ref> <ref>PMID:18692962</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Cannabinoid receptors are both therapeutically attractive and are interesting model systems for structure-based methods. Here we investigated topical questions in library docking using the CB2 receptor. While a CB1R docking campaign found potent but nonselective ligands, here subtype selective ligands were found by targeting polar residues. Hit rates and hit affinities improved with library size, but docking against active and inactive receptor states did not reliably bias toward agonists or antagonists. Cryo-EM structures of two of the new agonists superposed well on the docking predictions. Structure-based optimization led to 10- to 140-fold improvements within three series, consistent with well-behaved ligands. Hit rates with an explicit 2.6 billion molecule library resembled those of an implied 11 billion molecule library from a building-block method, supporting the latter's ability to explore this space, though higher affinities were discovered from the explicit set. Implications for future studies are considered.
-Authors: Sacco, M., Wu, C., Singal, B., Skiniotis, G.
+Library Docking for Cannabinoid-2 Receptor Ligands.,Rachman MM, Iliopoulos-Tsoutsouvas C, Sacco MD, Xu X, Wu CG, Santos E, Glenn IS, Paris L, Cahill MK, Ganapathy S, Tummino TA, Moroz YS, Radchenko DS, Okorie M, Tawfik VL, Irwin JJ, Makriyannis A, Skiniotis G, Shoichet BK J Med Chem. 2026 Jul 3. doi: 10.1021/acs.jmedchem.6c00835. PMID:42397716<ref>PMID:42397716</ref>
-Description: Locally refined cryo-EM structure of human cannabinoid receptor 2 with agonist ''5249
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Singal, B]]
+<div class="pdbe-citations 12iy" style="background-color:#fffaf0;"></div>
-[[Category: Sacco, M]]
+== References ==
-[[Category: Wu, C]]
+<references/>
-[[Category: Skiniotis, G]]
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Sacco M]]
+[[Category: Singal B]]
+[[Category: Skiniotis G]]
+[[Category: Wu C]]