1khc: Difference between revisions

Revision as of 21:47, 24 January 2018

Crystal Structure of the PWWP Domain of Mammalian DNA Methyltransferase Dnmt3b

Structural highlights

1khc is a 1 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:	UNX
Gene:	Dnmt3b (LK3 transgenic mice)
Activity:	DNA (cytosine-5-)-methyltransferase, with EC number 2.1.1.37
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[DNM3B_MOUSE] 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. 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. Function as transcriptional corepressor by associating with ZHX1 (By similarity).^[1] ^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

The PWWP domain is a weakly conserved sequence motif found in > 60 eukaryotic proteins, including the mammalian DNA methyltransferases Dnmt3a and Dnmt3b. These proteins often contain other chromatin-association domains. A 135-residue PWWP domain from mouse Dnmt3b (amino acids 223--357) has been structurally characterized at 1.8 A resolution. The N-terminal half of this domain resembles a barrel-like five-stranded structure, whereas the C-terminal half contains a five-helix bundle. The two halves are packed against each other to form a single structural module that exhibits a prominent positive electrostatic potential. The PWWP domain alone binds DNA in vitro, probably through its basic surface. We also show that recombinant Dnmt3b2 protein (a splice variant of Dnmt3b) and two N-terminal deletion mutants (Delta218 and Delta369) have approximately equal methyl transfer activity on unmethylated and hemimethylated CpG-containing oligonucleotides. The Delta218 protein, which includes the PWWP domain, binds DNA more strongly than Delta369, which lacks the PWWP domain.

The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds.,Qiu C, Sawada K, Zhang X, Cheng X Nat Struct Biol. 2002 Mar;9(3):217-24. PMID:11836534^[7]

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

References

↑ Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999 Oct 29;99(3):247-57. PMID:10555141
↑ Gowher H, Jeltsch A. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases. J Biol Chem. 2002 Jun 7;277(23):20409-14. Epub 2002 Mar 27. PMID:11919202 doi:https://dx.doi.org/10.1074/jbc.M202148200
↑ Takeshima H, Suetake I, Shimahara H, Ura K, Tate S, Tajima S. Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA. J Biochem. 2006 Mar;139(3):503-15. PMID:16567415 doi:https://dx.doi.org/139/3/503
↑ Linhart HG, Lin H, Yamada Y, Moran E, Steine EJ, Gokhale S, Lo G, Cantu E, Ehrich M, He T, Meissner A, Jaenisch R. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev. 2007 Dec 1;21(23):3110-22. PMID:18056424 doi:https://dx.doi.org/10.1101/gad.1594007
↑ Kim SH, Park J, Choi MC, Park JH, Kim HP, Lee JH, Oh DY, Im SA, Bang YJ, Kim TY. DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription. Int J Biochem Cell Biol. 2008;40(11):2462-71. doi: 10.1016/j.biocel.2008.04.018. , Epub 2008 May 18. PMID:18567530 doi:https://dx.doi.org/10.1016/j.biocel.2008.04.018
↑ Qiu C, Sawada K, Zhang X, Cheng X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 2002 Mar;9(3):217-24. PMID:11836534 doi:10.1038/nsb759
↑ Qiu C, Sawada K, Zhang X, Cheng X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 2002 Mar;9(3):217-24. PMID:11836534 doi:10.1038/nsb759

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Okano M, Bell DW, Haber DA, Li E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell. 1999 Oct 29;99(3):247-57. PMID:10555141

[2] Gowher H, Jeltsch A. Molecular enzymology of the catalytic domains of the Dnmt3a and Dnmt3b DNA methyltransferases. J Biol Chem. 2002 Jun 7;277(23):20409-14. Epub 2002 Mar 27. PMID:11919202 doi:https://dx.doi.org/10.1074/jbc.M202148200

[3] Takeshima H, Suetake I, Shimahara H, Ura K, Tate S, Tajima S. Distinct DNA methylation activity of Dnmt3a and Dnmt3b towards naked and nucleosomal DNA. J Biochem. 2006 Mar;139(3):503-15. PMID:16567415 doi:https://dx.doi.org/139/3/503

[4] Linhart HG, Lin H, Yamada Y, Moran E, Steine EJ, Gokhale S, Lo G, Cantu E, Ehrich M, He T, Meissner A, Jaenisch R. Dnmt3b promotes tumorigenesis in vivo by gene-specific de novo methylation and transcriptional silencing. Genes Dev. 2007 Dec 1;21(23):3110-22. PMID:18056424 doi:https://dx.doi.org/10.1101/gad.1594007

[5] Kim SH, Park J, Choi MC, Park JH, Kim HP, Lee JH, Oh DY, Im SA, Bang YJ, Kim TY. DNA methyltransferase 3B acts as a co-repressor of the human polycomb protein hPc2 to repress fibroblast growth factor receptor 3 transcription. Int J Biochem Cell Biol. 2008;40(11):2462-71. doi: 10.1016/j.biocel.2008.04.018. , Epub 2008 May 18. PMID:18567530 doi:https://dx.doi.org/10.1016/j.biocel.2008.04.018

[6] Qiu C, Sawada K, Zhang X, Cheng X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 2002 Mar;9(3):217-24. PMID:11836534 doi:10.1038/nsb759

[7] Qiu C, Sawada K, Zhang X, Cheng X. The PWWP domain of mammalian DNA methyltransferase Dnmt3b defines a new family of DNA-binding folds. Nat Struct Biol. 2002 Mar;9(3):217-24. PMID:11836534 doi:10.1038/nsb759

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@@ Line 1: / Line 1: @@
 ==Crystal Structure of the PWWP Domain of Mammalian DNA Methyltransferase Dnmt3b==
 <StructureSection load='1khc' size='340' side='right' caption='[[1khc]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Dnmt3b ([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=1khc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1khc OCA], [http://pdbe.org/1khc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1khc RCSB], [http://www.ebi.ac.uk/pdbsum/1khc 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=1khc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1khc OCA], [http://pdbe.org/1khc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1khc RCSB], [http://www.ebi.ac.uk/pdbsum/1khc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1khc ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 14: / Line 15: @@
 Check<jmol>
    <jmolCheckbox>
-     <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/1khc_consurf.spt"</scriptWhenChecked>
+     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/1khc_consurf.spt"</scriptWhenChecked>
      <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
      <text>to colour the structure by Evolutionary Conservation</text>
@@ Line 29: / Line 30: @@
 </div>
 <div class="pdbe-citations 1khc" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[DNA methyltransferase|DNA methyltransferase]]
 == References ==
 <references/>

1khc: Difference between revisions

Revision as of 21:47, 24 January 2018

Crystal Structure of the PWWP Domain of Mammalian DNA Methyltransferase Dnmt3b

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

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