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==Crystal structure of YTHDF2 with compound YLI_DF_042== | ==Crystal structure of YTHDF2 with compound YLI_DF_042== | ||
<StructureSection load='7zg4' size='340' side='right'caption='[[7zg4]]' scene=''> | <StructureSection load='7zg4' size='340' side='right'caption='[[7zg4]], [[Resolution|resolution]] 2.01Å' 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=7ZG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZG4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7zg4]] 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=7ZG4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7ZG4 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=7zg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zg4 OCA], [https://pdbe.org/7zg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zg4 RCSB], [https://www.ebi.ac.uk/pdbsum/7zg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zg4 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]] 2.01Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IQL:N-methylpyrimidine-2-carboximidamide'>IQL</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=7zg4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7zg4 OCA], [https://pdbe.org/7zg4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7zg4 RCSB], [https://www.ebi.ac.uk/pdbsum/7zg4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7zg4 ProSAT]</span></td></tr> | |||
</table> | </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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7zg4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Caflisch A]] | [[Category: Caflisch A]] | ||
[[Category: Li Y]] | [[Category: Li Y]] | ||
[[Category: Nai F]] | [[Category: Nai F]] | ||
Latest revision as of 16:32, 1 February 2024
Crystal structure of YTHDF2 with compound YLI_DF_042Crystal structure of YTHDF2 with compound YLI_DF_042
Structural highlights
FunctionYTHD2_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.[1] [2] Publication Abstract from PubMedWe 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[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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