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6y4g
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 6y4g is ON HOLD Authors: Bedi, R.K., Omori, E., Caflisch, A. Description: Crystal structure of the human METTL3-METTL14 complex bound to Sinefungin...) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of the human METTL3-METTL14 complex bound to Sinefungin== | |
| + | <StructureSection load='6y4g' size='340' side='right'caption='[[6y4g]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6y4g]] 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=6Y4G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6Y4G 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]] 1.9Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=SFG:SINEFUNGIN'>SFG</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=6y4g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6y4g OCA], [https://pdbe.org/6y4g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6y4g RCSB], [https://www.ebi.ac.uk/pdbsum/6y4g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6y4g ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/MET14_HUMAN MET14_HUMAN] N6-methyltransferase that methylates adenosine residues of some mRNAs and acts as a regulator of the circadian clock and differentiation of embryonic stem cells. N6-methyladenosine (m6A), which takes place at the 5'-[AG]GAC-3' consensus sites of some mRNAs, plays a role in the efficiency of mRNA splicing, processing and mRNA stability (PubMed:24316715, PubMed:24407421, PubMed:25719671). M6A regulates the length of the circadian clock: acts as a early pace-setter in the circadian loop. M6A also acts as a regulator of mRNA stability: in embryonic stem cells (ESCs), m6A methylation of mRNAs encoding key naive pluripotency-promoting transcripts results in transcript destabilization (By similarity).[UniProtKB:Q3UIK4]<ref>PMID:24316715</ref> <ref>PMID:24407421</ref> <ref>PMID:25719671</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The RNA methylase METTL3 catalyzes the transfer of a methyl group from the cofactor S-adenosyl-L-methionine (SAM) to the N(6) atom of adenine. We have screened a library of 4000 analogues and derivatives of the adenosine moiety of SAM by high-throughput docking into METTL3. Two series of adenine derivatives were identified in silico, and the binding mode of six of the predicted inhibitors was validated by protein crystallography. Two compounds, one for each series, show good ligand efficiency. We propose a route for their further development into potent and selective inhibitors of METTL3. | ||
| - | + | Small-Molecule Inhibitors of METTL3, the Major Human Epitranscriptomic Writer.,Bedi RK, Huang D, Eberle SA, Wiedmer L, Sledz P, Caflisch A ChemMedChem. 2020 May 6;15(9):744-748. doi: 10.1002/cmdc.202000011. Epub 2020 Mar, 23. PMID:32159918<ref>PMID:32159918</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6y4g" style="background-color:#fffaf0;"></div> |
| - | [[Category: Caflisch | + | == References == |
| - | [[Category: | + | <references/> |
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Bedi RK]] | ||
| + | [[Category: Caflisch A]] | ||
| + | [[Category: Omori E]] | ||
Current revision
Crystal structure of the human METTL3-METTL14 complex bound to Sinefungin
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