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==Crystal structure of human DNMT1(646-1600) in complex with DNA== | ==Crystal structure of human DNMT1(646-1600) in complex with DNA== | ||
<StructureSection load='3pta' size='340' side='right' caption='[[3pta]], [[Resolution|resolution]] 3.60Å' scene=''> | <StructureSection load='3pta' size='340' side='right'caption='[[3pta]], [[Resolution|resolution]] 3.60Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3pta]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3pta]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PTA OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PTA FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | </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=ZN:ZINC+ION'>ZN</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3pt6|3pt6]], [[3pt9|3pt9]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3pt6|3pt6]], [[3pt9|3pt9]]</div></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNMT1, AIM, CXXC9, DNMT ([ | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">DNMT1, AIM, CXXC9, DNMT ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | ||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.37 2.1.1.37] </span></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3pta FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pta OCA], [https://pdbe.org/3pta PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pta RCSB], [https://www.ebi.ac.uk/pdbsum/3pta PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pta ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Disease == | == Disease == | ||
[[ | [[https://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:[https://omim.org/entry/614116 614116]]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.<ref>PMID:21532572</ref> | ||
== Function == | == Function == | ||
[[ | [[https://www.uniprot.org/uniprot/DNMT1_HUMAN DNMT1_HUMAN]] Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B 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.<ref>PMID:16357870</ref> <ref>PMID:18754681</ref> <ref>PMID:18413740</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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==See Also== | ==See Also== | ||
*[[DNA methyltransferase|DNA methyltransferase]] | *[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
| Line 31: | Line 31: | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | [[Category: Human]] | ||
[[Category: Large Structures]] | |||
[[Category: Patel, D J]] | [[Category: Patel, D J]] | ||
[[Category: Song, J]] | [[Category: Song, J]] | ||
Revision as of 11:54, 25 May 2022
Crystal structure of human DNMT1(646-1600) in complex with DNACrystal structure of human DNMT1(646-1600) in complex with DNA
Structural highlights
Disease[DNMT1_HUMAN] Defects in DNMT1 are the cause of hereditary sensory neuropathy type 1E (HSN1E) [MIM:614116]. A neurodegenerative disorder characterized by adult onset of progressive peripheral sensory loss associated with progressive hearing impairment and early-onset dementia.[1] Function[DNMT1_HUMAN] Methylates CpG residues. Preferentially methylates hemimethylated DNA. Associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand, that is essential for epigenetic inheritance. Associates with chromatin during G2 and M phases to maintain DNA methylation independently of replication. It is responsible for maintaining methylation patterns established in development. DNA methylation is coordinated with methylation of histones. Mediates transcriptional repression by direct binding to HDAC2. In association with DNMT3B 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.[2] [3] [4] Publication Abstract from PubMedMaintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1). We have solved structures of mouse DNMT1 composed of CXXC, tandem bromo-adjacent homology (BAH1/2) and methyltransferase domains bound to DNA containing unmethylated CpG sites. The CXXC specifically binds to unmethylated CpG dinucleotide and positions the CXXC-BAH1 linker between the DNA and the active site of DNMT1, thereby preventing de novo methylation. In addition, a loop projecting from BAH2 interacts with the target recognition domain (TRD) of the methyltransferase, stabilizing the TRD in a retracted position, and preventing it from inserting into the DNA major groove. Our studies identify an autoinhibitory mechanism, whereby occlusion of unmethylated CpG dinucleotides from de novo methylation ensures that only hemimethylated CpG dinucleotides gain access to the active site. Structure of DNMT1-DNA Complex Reveals a Role for Autoinhibition in Maintenance DNA Methylation.,Song J, Rechkoblit O, Bestor TH, Patel DJ Science. 2010 Dec 16. PMID:21163962[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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