9pfd | pdb_00009pfd

RMI1-RMI2 bound to synthetic peptide P4Ser

spinqualitylabelsall models 9pfd, resolution 2.01Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9pfd is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.008Å Ligands: NH2 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

Proteopedia Page Contributors and Editors (what is this?)

OCA