View source for 6kdb


==Crystal structure of human DNMT3B-DNMT3L in complex with DNA containing CpGpT site==
<StructureSection load='6kdb' size='340' side='right'caption='[[6kdb]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6kdb]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KDB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6KDB 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]] 2.862&#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></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=6kdb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kdb OCA], [https://pdbe.org/6kdb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6kdb RCSB], [https://www.ebi.ac.uk/pdbsum/6kdb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6kdb ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/DNM3B_HUMAN DNM3B_HUMAN] ICF syndrome. The disease is caused by mutations affecting the gene represented in this entry.<ref>PMID:10647011</ref> <ref>PMID:10555141</ref> <ref>PMID:10588719</ref> <ref>PMID:11102980</ref> <ref>PMID:15580563</ref> 
== Function ==
[https://www.uniprot.org/uniprot/DNM3B_HUMAN DNM3B_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. May preferentially methylates nucleosomal DNA within the nucleosome core region. May function as transcriptional co-repressor by associating with CBX4 and independently of DNA methylation. Seems to be involved in gene silencing (By similarity). In association with DNMT1 and via the recruitment of CTCFL/BORIS, involved in activation of BAG1 gene expression by modulating dimethylation of promoter histone H3 at H3K4 and H3K9. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Function as transcriptional corepressor by associating with ZHX1.<ref>PMID:16357870</ref> <ref>PMID:17303076</ref> <ref>PMID:18413740</ref> <ref>PMID:18567530</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
DNA methyltransferases are primary enzymes for cytosine methylation at CpG sites of epigenetic gene regulation in mammals. De novo methyltransferases DNMT3A and DNMT3B create DNA methylation patterns during development, but how they differentially implement genomic DNA methylation patterns is poorly understood. Here, we report crystal structures of the catalytic domain of human DNMT3B-3L complex, noncovalently bound with and without DNA of different sequences. Human DNMT3B uses two flexible loops to enclose DNA and employs its catalytic loop to flip out the cytosine base. As opposed to DNMT3A, DNMT3B specifically recognizes DNA with CpGpG sites via residues Asn779 and Lys777 in its more stable and well-ordered target recognition domain loop to facilitate processive methylation of tandemly repeated CpG sites. We also identify a proton wire water channel for the final deprotonation step, revealing the complete working mechanism for cytosine methylation by DNMT3B and providing the structural basis for DNMT3B mutation-induced hypomethylation in immunodeficiency, centromere instability and facial anomalies syndrome.

Structural insights into CpG-specific DNA methylation by human DNA methyltransferase 3B.,Lin CC, Chen YP, Yang WZ, Shen JCK, Yuan HS Nucleic Acids Res. 2020 Feb 21. pii: 5742902. doi: 10.1093/nar/gkaa111. PMID:32083663<ref>PMID:32083663</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6kdb" style="background-color:#fffaf0;"></div>

==See Also==
*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Synthetic construct]]
[[Category: Chen Y-P]]
[[Category: Lin C-C]]
[[Category: Shen C-K]]
[[Category: Yang W-Z]]
[[Category: Yuan HS]]