7lky
From Proteopedia
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| - | ==== | + | ==Crystal Structure of PHF1 Tudor domain in complex with a peptidomimetic ligand UNC6641== |
| - | <StructureSection load='7lky' size='340' side='right'caption='[[7lky]]' scene=''> | + | <StructureSection load='7lky' size='340' side='right'caption='[[7lky]], [[Resolution|resolution]] 1.85Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7lky]] is a 16 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=7LKY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7LKY FirstGlance]. <br> |
| - | </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=7lky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lky OCA], [https://pdbe.org/7lky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lky RCSB], [https://www.ebi.ac.uk/pdbsum/7lky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lky ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.85Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=Y57:N~6~-(2-phenylethyl)-N~6~-propan-2-yl-L-lysine'>Y57</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=7lky FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7lky OCA], [https://pdbe.org/7lky PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7lky RCSB], [https://www.ebi.ac.uk/pdbsum/7lky PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7lky ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/PHF1_HUMAN PHF1_HUMAN] Transcriptional repressor. May promote methylation of histone H3 on 'Lys-27' by the PRC2/EED-EZH2 complex.<ref>PMID:18086877</ref> <ref>PMID:18285464</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Plant homeodomain finger protein 1 (PHF1) is an accessory component of the gene silencing complex polycomb repressive complex 2 and recognizes the active chromatin mark, trimethylated lysine 36 of histone H3 (H3K36me3). In addition to its role in transcriptional regulation, PHF1 has been implicated as a driver of endometrial stromal sarcoma and fibromyxoid tumors. We report the discovery and characterization of UNC6641, a peptidomimetic antagonist of the PHF1 Tudor domain which was optimized through in silico modeling and incorporation of non-natural amino acids. UNC6641 binds the PHF1 Tudor domain with a K(d) value of 0.96 +/- 0.03 muM while also binding the related protein PHF19 with similar potency. A crystal structure of PHF1 in complex with UNC6641, along with NMR and site-directed mutagenesis data, provided insight into the binding mechanism and requirements for binding. Additionally, UNC6641 enabled the development of a high-throughput assay to identify small molecule binders of PHF1. | ||
| + | |||
| + | Discovery of an H3K36me3-Derived Peptidomimetic Ligand with Enhanced Affinity for Plant Homeodomain Finger Protein 1 (PHF1).,Engelberg IA, Liu J, Norris-Drouin JL, Cholensky SH, Ottavi SA, Frye SV, Kutateladze TG, James LI J Med Chem. 2021 Jun 24;64(12):8510-8522. doi: 10.1021/acs.jmedchem.1c00430. Epub , 2021 May 17. PMID:33999620<ref>PMID:33999620</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7lky" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Synthetic construct]] |
| + | [[Category: Kutateladze TG]] | ||
| + | [[Category: Liu J]] | ||
Current revision
Crystal Structure of PHF1 Tudor domain in complex with a peptidomimetic ligand UNC6641
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