3pta: Difference between revisions

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<StructureSection load='3pta' size='340' side='right'caption='[[3pta]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
<StructureSection load='3pta' size='340' side='right'caption='[[3pta]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<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>
<table><tr><td colspan='2'>[[3pta]] is a 3 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=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" id="ligandDat"><scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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]] 3.6&#8491;</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='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='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'>[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'>[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>
<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>
[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> 
[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;">
== Publication Abstract from PubMed ==
Maintenance 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<ref>PMID:21163962</ref>
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3pta" style="background-color:#fffaf0;"></div>


==See Also==
==See Also==
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__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Human]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Patel, D J]]
[[Category: Patel DJ]]
[[Category: Song, J]]
[[Category: Song J]]
[[Category: Dnmt1]]
[[Category: Maintenance dna methylation]]
[[Category: Transferase-dna complex]]

Latest revision as of 13:43, 21 February 2024

Crystal structure of human DNMT1(646-1600) in complex with DNACrystal structure of human DNMT1(646-1600) in complex with DNA

Structural highlights

3pta is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 3.6Å
Ligands:,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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]

See Also

References

  1. ↑ Klein CJ, Botuyan MV, Wu Y, Ward CJ, Nicholson GA, Hammans S, Hojo K, Yamanishi H, Karpf AR, Wallace DC, Simon M, Lander C, Boardman LA, Cunningham JM, Smith GE, Litchy WJ, Boes B, Atkinson EJ, Middha S, B Dyck PJ, Parisi JE, Mer G, Smith DI, Dyck PJ. Mutations in DNMT1 cause hereditary sensory neuropathy with dementia and hearing loss. Nat Genet. 2011 Jun;43(6):595-600. Epub 2011 May 1. PMID:21532572 doi:10.1038/ng.830
  2. ↑ Vire E, Brenner C, Deplus R, Blanchon L, Fraga M, Didelot C, Morey L, Van Eynde A, Bernard D, Vanderwinden JM, Bollen M, Esteller M, Di Croce L, de Launoit Y, Fuks F. The Polycomb group protein EZH2 directly controls DNA methylation. Nature. 2006 Feb 16;439(7078):871-4. Epub 2005 Dec 14. PMID:16357870 doi:10.1038/nature04431
  3. ↑ Pradhan M, Esteve PO, Chin HG, Samaranayke M, Kim GD, Pradhan S. CXXC domain of human DNMT1 is essential for enzymatic activity. Biochemistry. 2008 Sep 23;47(38):10000-9. doi: 10.1021/bi8011725. Epub 2008 Aug, 29. PMID:18754681 doi:10.1021/bi8011725
  4. ↑ Sun L, Huang L, Nguyen P, Bisht KS, Bar-Sela G, Ho AS, Bradbury CM, Yu W, Cui H, Lee S, Trepel JB, Feinberg AP, Gius D. DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment of CTCFL/BORIS and modulation of promoter histone methylation. Cancer Res. 2008 Apr 15;68(8):2726-35. PMID:18413740 doi:68/8/2726

3pta, resolution 3.60Å

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