4da4

From Proteopedia

(Difference between revisions)

Revision as of 03:56, 5 August 2016

Structure of mouse DNMT1 (731-1602) bound to hemimethylated CpG DNA

Structural highlights

4da4 is a 6 chain structure with sequence from Lk3 transgenic mice. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, ,
NonStd Res:	,
Gene:	Dnmt1, Dnmt, Met1, Uim (LK3 transgenic mice)
Activity:	DNA (cytosine-5-)-methyltransferase, with EC number 2.1.1.37
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DNMT1_MOUSE] 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.^[1] ^[2] ^[3]

Publication Abstract from PubMed

DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation. We report on the crystal structure of a productive covalent mouse DNMT1(731-1602)-DNA complex containing a central hemimethylated CpG site. The methyl group of methylcytosine is positioned within a shallow hydrophobic concave surface, whereas the cytosine on the target strand is looped out and covalently anchored within the catalytic pocket. The DNA is distorted at the hemimethylated CpG step, with side chains from catalytic and recognition loops inserting through both grooves to fill an intercalation-type cavity associated with a dual base flip-out on partner strands. Structural and biochemical data establish how a combination of active and autoinhibitory mechanisms ensures the high fidelity of DNMT1-mediated maintenance DNA methylation.

Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation.,Song J, Teplova M, Ishibe-Murakami S, Patel DJ Science. 2012 Feb 10;335(6069):709-12. PMID:22323818^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell. 2001 Mar 23;104(6):829-38. PMID:11290321
↑ Easwaran HP, Schermelleh L, Leonhardt H, Cardoso MC. Replication-independent chromatin loading of Dnmt1 during G2 and M phases. EMBO Rep. 2004 Dec;5(12):1181-6. PMID:15550930 doi:http://dx.doi.org/10.1038/sj.embor.7400295
↑ Schermelleh L, Haemmer A, Spada F, Rosing N, Meilinger D, Rothbauer U, Cardoso MC, Leonhardt H. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 2007;35(13):4301-12. Epub 2007 Jun 18. PMID:17576694 doi:http://dx.doi.org/10.1093/nar/gkm432
↑ Song J, Teplova M, Ishibe-Murakami S, Patel DJ. Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation. Science. 2012 Feb 10;335(6069):709-12. PMID:22323818 doi:http://dx.doi.org/10.1126/science.1214453

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4da4"

@@ Line 1: / Line 1: @@
 ==Structure of mouse DNMT1 (731-1602) bound to hemimethylated CpG DNA==
 <StructureSection load='4da4' size='340' side='right' caption='[[4da4]], [[Resolution|resolution]] 2.60&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4da4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA4 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4da4]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4DA4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4DA4 FirstGlance]. <br>
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
 <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=5CM:5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>5CM</scene>, <scene name='pdbligand=C49:4-THIO,5-FLUORO,5-METHYL-2-DEOXY-CYTIDINE-5-MONOPHOSPHATE'>C49</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dnmt1, Dnmt, Met1, Uim ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dnmt1, Dnmt, Met1, Uim ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/DNA_(cytosine-5-)-methyltransferase DNA (cytosine-5-)-methyltransferase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4da4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da4 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4da4 RCSB], [http://www.ebi.ac.uk/pdbsum/4da4 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4da4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4da4 OCA], [http://pdbe.org/4da4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4da4 RCSB], [http://www.ebi.ac.uk/pdbsum/4da4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4da4 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4da4" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 26: / Line 28: @@
 __TOC__
 </StructureSection>
-[[Category: Mus musculus]]
+[[Category: Lk3 transgenic mice]]
 [[Category: Patel, D J]]
 [[Category: Song, J]]

4da4

From Proteopedia

Revision as of 03:56, 5 August 2016

Structure of mouse DNMT1 (731-1602) bound to hemimethylated CpG DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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