6f0g: Difference between revisions
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<StructureSection load='6f0g' size='340' side='right'caption='[[6f0g]], [[Resolution|resolution]] 2.30Å' scene=''> | <StructureSection load='6f0g' size='340' side='right'caption='[[6f0g]], [[Resolution|resolution]] 2.30Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6f0g]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6f0g]] is a 4 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=6F0G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F0G FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | |||
<tr id=' | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6f0g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f0g OCA], [https://pdbe.org/6f0g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f0g RCSB], [https://www.ebi.ac.uk/pdbsum/6f0g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f0g ProSAT]</span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ASF1A_HUMAN 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.<ref>PMID:10759893</ref> <ref>PMID:11897662</ref> <ref>PMID:12842904</ref> <ref>PMID:14718166</ref> <ref>PMID:15621527</ref> <ref>PMID:16151251</ref> <ref>PMID:15664198</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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</div> | </div> | ||
<div class="pdbe-citations 6f0g" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 6f0g" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Anti-silencing factor 3D structures|Anti-silencing factor 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Andreani | [[Category: Andreani J]] | ||
[[Category: Gaubert A]] | |||
[[Category: Gaubert | [[Category: Guerois R]] | ||
[[Category: Guerois | [[Category: Guichard B]] | ||
[[Category: Guichard | [[Category: Le Du MH]] | ||
[[Category: | [[Category: Ochsenbein F]] | ||
[[Category: | [[Category: Richet N]] | ||
[[Category: | |||
Latest revision as of 15:23, 9 May 2024
Crystal structure ASF1-ip3Crystal structure ASF1-ip3
Structural highlights
FunctionASF1A_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.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedAnti-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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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