9pfd: Difference between revisions

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'''Unreleased structure'''


The entry 9pfd is ON HOLD
==RMI1-RMI2 bound to synthetic peptide P4Ser==
<StructureSection load='9pfd' size='340' side='right'caption='[[9pfd]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9pfd]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9PFD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9PFD 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]] 2.008&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NH2:AMINO+GROUP'>NH2</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=9pfd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9pfd OCA], [https://pdbe.org/9pfd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9pfd RCSB], [https://www.ebi.ac.uk/pdbsum/9pfd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9pfd ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
FANCM-RMI is a protein-protein interaction that maintains genome stability during DNA repair events in cancers that rely on the Alternative Lengthening of Telomeres (ALT) pathway for survival. We report the first valid chemical inhibitors of the FANCM-RMI interaction discovered by screening cyclic peptides via mRNA display. These inhibitors engage the FANCM-binding pocket of RMI1/2 with nanomolar affinity (K(D) = 2-10 nM) and are potent disruptors of the FANCM-RMI interaction (IC(50) = 54-104 nM). X-ray crystallography and alanine scanning reveal novel binding modes and interactions between the cyclic peptides and RMI1/2 that drive high-potency inhibition. Co-immunoprecipitation studies confirm the complete disruption of the native interaction in whole osteosarcoma cell lysates. These inhibitors represent the first validated RMI binders toward developing chemical tools for interrogating the mechanistic roles of FANCM-RMI in mediating genome stability and provide a much-anticipated starting point to accelerate the development of FANCM-RMI inhibitors for intervention against ALT-driven cancers.


Authors:  
Potent Cyclic Peptide Inhibitors Disrupt the FANCM-RMI Interaction.,Alcock LJ, Gao T, Bythell-Douglas R, Gao J, Krishna Sudhakar H, Huang T, Young R, Vu QN, Deshpande C, Wilkinson-White LE, Passioura T, Pickett HA, Deans AJ, Lau YH J Med Chem. 2025 Jun 26;68(12):12615-12625. doi: 10.1021/acs.jmedchem.5c00365. , Epub 2025 Jun 6. PMID:40479515<ref>PMID:40479515</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 9pfd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Alcock LJ]]
[[Category: Bythell-Douglas R]]
[[Category: Deshpande C]]
[[Category: Lau YH]]
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