6f57: Difference between revisions

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OCA

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-'''Unreleased structure'''
-The entry 6f57 is ON HOLD
+==Crystal structure of DNMT3A-DNMT3L in complex with single CpG-containing DNA==
+<StructureSection load='6f57' size='340' side='right'caption='[[6f57]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[6f57]] 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=6F57 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6F57 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]] 3.098&#8491;</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=Z:1-(2-DEOXY-5-O-PHOSPHONO-BETA-D-ERYTHRO-PENTOFURANOSYL)PYRIMIDIN-2(1H)-ONE'>Z</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=6f57 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6f57 OCA], [https://pdbe.org/6f57 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6f57 RCSB], [https://www.ebi.ac.uk/pdbsum/6f57 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6f57 ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/DNM3A_HUMAN DNM3A_HUMAN] Required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. DNA methylation is coordinated with methylation of histones. It modifies DNA in a non-processive manner and also methylates non-CpG sites. May preferentially methylate DNA linker between 2 nucleosomal cores and is inhibited by histone H1. Plays a role in paternal and maternal imprinting. Required for methylation of most imprinted loci in germ cells. Acts as a transcriptional corepressor for ZNF238. Can actively repress transcription through the recruitment of HDAC activity (By similarity).<ref>PMID:16357870</ref>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) at cytosines is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive. Here we report a 2.65-angstrom crystal structure of the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides, with the target sites separated by 14 base pairs within the same DNA duplex. The DNMT3A-DNA interaction involves a target recognition domain, a catalytic loop, and DNMT3A homodimeric interface. Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. Haematological cancer-associated somatic mutations of the substrate-binding residues decrease DNMT3A activity, induce CpG hypomethylation, and promote transformation of haematopoietic cells. Together, our study reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease.
-Authors: Zhang, Z.M., Song, J.
+Structural basis for DNMT3A-mediated de novo DNA methylation.,Zhang ZM, Lu R, Wang P, Yu Y, Chen D, Gao L, Liu S, Ji D, Rothbart SB, Wang Y, Wang GG, Song J Nature. 2018 Feb 15;554(7692):387-391. doi: 10.1038/nature25477. Epub 2018 Feb 7. PMID:29414941<ref>PMID:29414941</ref>
-Description: Crystal structure of DNMT3A-DNMT3L in complex with single CpG-containing DNA
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Song, J]]
+<div class="pdbe-citations 6f57" style="background-color:#fffaf0;"></div>
-[[Category: Zhang, Z.M]]
+==See Also==
+*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Homo sapiens]]
+[[Category: Large Structures]]
+[[Category: Song J]]
+[[Category: Zhang ZM]]