12ja: Difference between revisions

From Proteopedia
Jump to navigationJump to search
← Older edit
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
OCA (talk | contribs)
Bots, Bureaucrats, journal, Administrators
3,328,572 edits
No edit summary
 
Line 1: Line 1:
'''Unreleased structure'''


The entry 12ja is ON HOLD  until Paper Publication
==Cryo-EM structure of human cannabinoid receptor 2-Gi complex with agonist '1029==
<StructureSection load='12ja' size='340' side='right'caption='[[12ja]], [[Resolution|resolution]] 2.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[12ja]] is a 4 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=12JA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=12JA 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]] 2.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1DB6:methyl+2-[(4-ethyl-3-morpholin-4-ylsulfonyl-phenyl)carbonyl-hexyl-amino]ethanoate'>A1DB6</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=12ja FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=12ja OCA], [https://pdbe.org/12ja PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=12ja RCSB], [https://www.ebi.ac.uk/pdbsum/12ja PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=12ja ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/GNAI1_HUMAN GNAI1_HUMAN] Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. The G(i) proteins are involved in hormonal regulation of adenylate cyclase: they inhibit the cyclase in response to beta-adrenergic stimuli. The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. May play a role in cell division.<ref>PMID:17635935</ref> <ref>PMID:17264214</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: Cryo-EM structure of human cannabinoid receptor 2-Gi complex with agonist ''1029
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Sacco, M]]
<div class="pdbe-citations 12ja" style="background-color:#fffaf0;"></div>
[[Category: Singal, B]]
== 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]]
Retrieved from "https://proteopedia.org/12ja"