View source for 7z54


==Crystal structure of YTHDF2 with compound YLI_DC1_006==
<StructureSection load='7z54' size='340' side='right'caption='[[7z54]], [[Resolution|resolution]] 1.82&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7z54]] is a 2 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=7Z54 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z54 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]] 1.82&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=OYT:9-cyclopropyl-~{N}-methyl-purin-6-amine'>OYT</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=7z54 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z54 OCA], [https://pdbe.org/7z54 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z54 RCSB], [https://www.ebi.ac.uk/pdbsum/7z54 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z54 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/YTHD2_HUMAN YTHD2_HUMAN] Specifically recognizes and binds N6-methyladenosine (m6A)-containing RNAs. M6A is a modification present at internal sites of mRNAs and some non-coding RNAs and plays a role in the efficiency of mRNA splicing, processing and stability. Acts as a regulator of mRNA stability: binding to m6A-containing mRNAs results in the localization of to mRNA decay sites, such as processing bodies (P-bodies), leading to mRNA degradation.<ref>PMID:22575960</ref> <ref>PMID:24284625</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We report 17 small-molecule ligands that compete with N6-methyladenosine (m(6)A) for binding to the m(6)A-reader domain of YTHDF2 (YT521-B homology domain family 2). We determined their binding mode at high resolution by X-ray crystallography and quantified their affinity by a fluorescence-based binding assay. 6-Cyclopropyluracil and a pyrazolopyrimidine derivative have favorable ligand efficiencies of 0.47 and 0.38 kcal mol(-1) per non-hydrogen atom, respectively. They represent useful starting points for hit optimization.

Fragment Ligands of the m(6)A-RNA Reader YTHDF2.,Nai F, Nachawati R, Zalesak F, Wang X, Li Y, Caflisch A ACS Med Chem Lett. 2022 Aug 17;13(9):1500-1509. doi:, 10.1021/acsmedchemlett.2c00303. eCollection 2022 Sep 8. PMID:36110386<ref>PMID:36110386</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7z54" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Caflisch A]]
[[Category: Dolbois A]]
[[Category: Li Y]]
[[Category: Nai F]]