8hyi

Crystal structure of human P-cadherin MEC12 (X dimer) in complex with 2-(2-methyl-5-phenyl-1H-indole-3-yl)ethan-1-amine

spinqualitylabelsall models 8hyi, resolution 2.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8hyi is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.85Å Ligands: 22R, CA, DMS Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease 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 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. 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. 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 Sep;32(9):e4744. doi: 10.1002/pro.4744. PMID:37531208 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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