6f0g

Crystal structure ASF1-ip3

spinqualitylabelsall models 6f0g, resolution 2.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6f0g is a 4 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 2.3Å Ligands: SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function ASF1A_HUMAN Histone chaperone that facilitates histone deposition and histone exchange and removal during nucleosome assembly and disassembly. Cooperates with chromatin assembly factor 1 (CAF-1) to promote replication-dependent chromatin assembly and with HIRA to promote replication-independent chromatin assembly. Required for the formation of senescence-associated heterochromatin foci (SAHF) and efficient senescence-associated cell cycle exit. Publication Abstract from PubMed Anti-silencing function 1 (ASF1) is a conserved H3-H4 histone chaperone involved in histone dynamics during replication, transcription, and DNA repair. Overexpressed in proliferating tissues including many tumors, ASF1 has emerged as a promising therapeutic target. Here, we combine structural, computational, and biochemical approaches to design peptides that inhibit the ASF1-histone interaction. Starting from the structure of the human ASF1-histone complex, we developed a rational design strategy combining epitope tethering and optimization of interface contacts to identify a potent peptide inhibitor with a dissociation constant of 3 nM. When introduced into cultured cells, the inhibitors impair cell proliferation, perturb cell-cycle progression, and reduce cell migration and invasion in a manner commensurate with their affinity for ASF1. Finally, we find that direct injection of the most potent ASF1 peptide inhibitor in mouse allografts reduces tumor growth. Our results open new avenues to use ASF1 inhibitors as promising leads for cancer therapy. Design on a Rational Basis of High-Affinity Peptides Inhibiting the Histone Chaperone ASF1.,Bakail M, Gaubert A, Andreani J, Moal G, Pinna G, Boyarchuk E, Gaillard MC, Courbeyrette R, Mann C, Thuret JY, Guichard B, Murciano B, Richet N, Poitou A, Frederic C, Le Du MH, Agez M, Roelants C, Gurard-Levin ZA, Almouzni G, Cherradi N, Guerois R, Ochsenbein F Cell Chem Biol. 2019 Nov 21;26(11):1573-1585.e10. doi:, 10.1016/j.chembiol.2019.09.002. Epub 2019 Sep 19. PMID:31543461 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Anti-silencing factor 3D structures

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