View source for 7yyj


==Tetragonal crystal structure of YTHDF1 YTH domain (544AVV546 mutant)==
<StructureSection load='7yyj' size='340' side='right'caption='[[7yyj]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7yyj]] 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=7YYJ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7YYJ 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]] 2.1&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=SCN:THIOCYANATE+ION'>SCN</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=7yyj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7yyj OCA], [https://pdbe.org/7yyj PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7yyj RCSB], [https://www.ebi.ac.uk/pdbsum/7yyj PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7yyj ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/YTHD1_HUMAN YTHD1_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.<ref>PMID:24284625</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing the m(6)A mark on mRNA and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present in the organization of the m(6)A-binding pocket. Here, we present new crystallographic structures of the YTH domain of YTHDF1, accompanied by computational studies, showing that this domain can exist in different stable conformations separated by a significant energetic barrier. During the transition, additional conformations are explored, with peculiar druggable pockets appearing and offering new opportunities for the design of YTH-interfering small molecules.

Pliability in the m(6)A-Binding Region Extends Druggability of YTH Domains.,Cazzanelli G, Dalle Vedove A, Spagnolli G, Terruzzi L, Colasurdo E, Boldrini A, Patsilinakos A, Sturlese M, Grottesi A, Biasini E, Provenzani A, Quattrone A, Lolli G J Chem Inf Model. 2024 Mar 11;64(5):1682-1690. doi: 10.1021/acs.jcim.4c00051. , Epub 2024 Feb 28. PMID:38417111<ref>PMID:38417111</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7yyj" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Cazzanelli G]]
[[Category: Dalle Vedove A]]
[[Category: Lolli G]]