8dkb
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal Structure of human YEATS4 in complex with Pfizer small molecule compound 3b== | |
| + | <StructureSection load='8dkb' size='340' side='right'caption='[[8dkb]], [[Resolution|resolution]] 2.58Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8dkb]] is a 8 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=8DKB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8DKB 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]] 2.58Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SJI:N-ethyl-1-{(3S,4S)-1-[(1-hydroxycyclohexyl)methyl]-3-methylpiperidin-4-yl}-2-methyl-1H-benzimidazole-5-carboxamide'>SJI</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=8dkb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8dkb OCA], [https://pdbe.org/8dkb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8dkb RCSB], [https://www.ebi.ac.uk/pdbsum/8dkb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8dkb ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/YETS4_HUMAN YETS4_HUMAN] Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when recruited to sites of DNA damage.<ref>PMID:14966270</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | A series of small-molecule YEATS4 binders have been discovered as part of an ongoing research effort to generate high-quality probe molecules for emerging and/or challenging epigenetic targets. Analogues such as 4d and 4e demonstrate excellent potency and selectivity for YEATS4 binding versus YEATS1,2,3 and exhibit good physical properties and in vitro safety profiles. A new X-ray crystal structure confirms direct binding of this chemical series to YEATS4 at the lysine acetylation recognition site of the YEATS domain. Multiple analogues engage YEATS4 with nanomolar potency in a whole-cell nanoluciferase bioluminescent resonance energy transfer assay. Rodent pharmacokinetic studies demonstrate the competency of several analogues as in vivo-capable binders. | ||
| - | + | Discovery of High-Affinity Small-Molecule Binders of the Epigenetic Reader YEATS4.,Londregan AT, Aitmakhanova K, Bennett J, Byrnes LJ, Canterbury DP, Cheng X, Christott T, Clemens J, Coffey SB, Dias JM, Dowling MS, Farnie G, Fedorov O, Fennell KF, Gamble V, Gileadi C, Giroud C, Harris MR, Hollingshead BD, Huber K, Korczynska M, Lapham K, Loria PM, Narayanan A, Owen DR, Raux B, Sahasrabudhe PV, Ruggeri RB, Saez LD, Stock IA, Thuma BA, Tsai A, Varghese AE J Med Chem. 2022 Dec 23. doi: 10.1021/acs.jmedchem.2c01421. PMID:36562986<ref>PMID:36562986</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8dkb" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Byrnes LJ]] | ||
| + | [[Category: Dias JM]] | ||
| + | [[Category: Varghese AH]] | ||
Current revision
Crystal Structure of human YEATS4 in complex with Pfizer small molecule compound 3b
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