8hyi: Difference between revisions
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The entry | ==Crystal structure of human P-cadherin MEC12 (X dimer) in complex with 2-(2-methyl-5-phenyl-1H-indole-3-yl)ethan-1-amine== | ||
<StructureSection load='8hyi' size='340' side='right'caption='[[8hyi]], [[Resolution|resolution]] 2.85Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8hyi]] is a 2 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=8HYI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8HYI 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]] 2.85Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=22R:2-(2-methyl-5-phenyl-1H-indole-3-yl)ethan-1-amine'>22R</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</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=8hyi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8hyi OCA], [https://pdbe.org/8hyi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8hyi RCSB], [https://www.ebi.ac.uk/pdbsum/8hyi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8hyi ProSAT]</span></td></tr> | |||
</table> | |||
== Disease == | |||
[https://www.uniprot.org/uniprot/CADH3_HUMAN CADH3_HUMAN] Hypotrichosis with juvenile macular degeneration;EEM syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. | |||
== Function == | |||
[https://www.uniprot.org/uniprot/CADH3_HUMAN CADH3_HUMAN] Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Small molecules that regulate protein-protein interactions can be valuable drugs; however, the development of such small molecules is challenging as the molecule must interfere with an interaction that often involves a large surface area. Herein, we propose that modulating the conformational ensemble of the proteins participating in a given interaction, rather than blocking the interaction by directly binding to the interface, is a relevant strategy for interfering with a protein-protein interaction. In this study, we applied this concept to P-cadherin, a cell surface protein forming homodimers that are essential for cell-cell adhesion in various biological contexts. We first determined the crystal structure of P-cadherin with a small molecule inhibitor whose inhibitory mechanism was unknown. Molecular dynamics simulations suggest that the inhibition of cell adhesion by this small molecule results from modulation of the conformational ensemble of P-cadherin. Our study demonstrates the potential of small molecules altering the conformation ensemble of a protein as inhibitors of biological relevant protein-protein interactions. This article is protected by copyright. All rights reserved. | |||
Modulation of a conformational ensemble by a small molecule that inhibits key protein-protein interactions involved in cell adhesion.,Senoo A, Nagatoishi S, Kuroda D, Ito S, Ueno G, Caaveiro JMM, Tsumoto K Protein Sci. 2023 Aug 2:e4744. doi: 10.1002/pro.4744. PMID:37531208<ref>PMID:37531208</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
[[Category: | <div class="pdbe-citations 8hyi" style="background-color:#fffaf0;"></div> | ||
[[Category: | == References == | ||
[[Category: Senoo | <references/> | ||
[[Category: | __TOC__ | ||
[[Category: Ueno | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Ito S]] | |||
[[Category: Nagatoishi S]] | |||
[[Category: Senoo A]] | |||
[[Category: Tsumoto K]] | |||
[[Category: Ueno G]] | |||
