5guv

From Proteopedia

(Difference between revisions)

Current revision

The crystal structure of mouse DNMT1 (731-1602) mutant - R1279D

Structural highlights

5guv is a 1 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 3.078Å
Ligands:
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

DNA methyltransferase-1 (DNMT1) plays a crucial role in the maintenance of genomic methylation patterns. The crystal structure of DNMT1 was determined in two different states in which the helix that follows the catalytic loop was either kinked (designated helix-kinked) or well folded (designated helix-straight state). Here, we show that the proper structural transition between these two states is required for DNMT1 activity. The mutations of N1248A and R1279D, which did not affect interactions between DNMT1 and substrates or cofactors, allosterically reduced enzymatic activities in vitro by decreasing kcat/ Km for AdoMet. The crystallographic data combined with molecular dynamic (MD) simulations indicated that the N1248A and R1279D mutants bias the catalytic helix to either the kinked or straight conformation. In addition, genetic complementation assays for the two mutants suggested that disturbing the conformational transition reduced DNMT1 activity in cells, which could act additively with existing DNMT inhibitors to decrease DNA methylation. Collectively, our studies provide molecular insights into conformational changes of the catalytic helix, which is essential for DNMT1 catalytic activity, and thus aid in better understanding the relationship between DNMT1 dynamic switching and enzymatic activity.

Biochemical Studies and Molecular Dynamic Simulations Reveal the Molecular Basis of Conformational Changes in DNA Methyltransferase-1.,Ye F, Kong X, Zhang H, Liu Y, Shao Z, Jin J, Cai Y, Zhang R, Li L, Zhang YW, Liu YC, Zhang C, Xie W, Yu K, Ding H, Zhao K, Chen S, Jiang H, Baylin SB, Luo C ACS Chem Biol. 2018 Mar 16;13(3):772-781. doi: 10.1021/acschembio.7b00890. Epub, 2018 Feb 8. PMID:29381856^[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
↑ Ye F, Kong X, Zhang H, Liu Y, Shao Z, Jin J, Cai Y, Zhang R, Li L, Zhang YW, Liu YC, Zhang C, Xie W, Yu K, Ding H, Zhao K, Chen S, Jiang H, Baylin SB, Luo C. Biochemical Studies and Molecular Dynamic Simulations Reveal the Molecular Basis of Conformational Changes in DNA Methyltransferase-1. ACS Chem Biol. 2018 Mar 16;13(3):772-781. doi: 10.1021/acschembio.7b00890. Epub, 2018 Feb 8. PMID:29381856 doi:http://dx.doi.org/10.1021/acschembio.7b00890

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/5guv"

Categories: Large Structures | Mus musculus | Chen SJ | Ye F

@@ Line 3: / Line 3: @@
 <StructureSection load='5guv' size='340' side='right'caption='[[5guv]], [[Resolution|resolution]] 3.08&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5guv]] is a 1 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=5GUV OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5GUV FirstGlance]. <br>
+<table><tr><td colspan='2'>[[5guv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5GUV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5GUV FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 3.078&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5gut|5gut]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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, 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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=5guv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5guv OCA], [https://pdbe.org/5guv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5guv RCSB], [https://www.ebi.ac.uk/pdbsum/5guv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5guv ProSAT]</span></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=5guv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5guv OCA], [http://pdbe.org/5guv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5guv RCSB], [http://www.ebi.ac.uk/pdbsum/5guv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5guv ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/DNMT1_MOUSE 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.<ref>PMID:11290321</ref> <ref>PMID:15550930</ref> <ref>PMID:17576694</ref>
+[https://www.uniprot.org/uniprot/DNMT1_MOUSE 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.<ref>PMID:11290321</ref> <ref>PMID:15550930</ref> <ref>PMID:17576694</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 23: / Line 21: @@
 ==See Also==
-*[[DNA methyltransferase|DNA methyltransferase]]
+*[[DNA methyltransferase 3D structures|DNA methyltransferase 3D structures]]
 == References ==
 <references/>
@@ Line 29: / Line 27: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Chen, S J]]
+[[Category: Chen SJ]]
-[[Category: Ye, F]]
+[[Category: Ye F]]
-[[Category: Mutant]]
-[[Category: Transferase]]

5guv

From Proteopedia

Current revision

The crystal structure of mouse DNMT1 (731-1602) mutant - R1279D

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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