2j2s: Difference between revisions

Revision as of 08:15, 4 May 2008

SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BINDING CXXC DOMAIN OF THE LEUKAEMIA-ASSOCIATED MLL HISTONE METHYLTRANSFERASE

OverviewOverview

Methylation of CpG dinucleotides is the major epigenetic modification of mammalian genomes, critical for regulating chromatin structure and gene activity. The mixed-lineage leukaemia (MLL) CXXC domain selectively binds nonmethyl-CpG DNA, and is required for transformation by MLL fusion proteins that commonly arise from recurrent chromosomal translocations in infant and secondary treatment-related acute leukaemias. To elucidate the molecular basis of nonmethyl-CpG DNA recognition, we determined the structure of the human MLL CXXC domain by multidimensional NMR spectroscopy. The CXXC domain has a novel fold in which two zinc ions are each coordinated tetrahedrally by four conserved cysteine ligands provided by two CGXCXXC motifs and two distal cysteine residues. We have identified the CXXC domain DNA binding interface by means of chemical shift perturbation analysis, cross-saturation transfer and site-directed mutagenesis. In particular, we have shown that residues in an extended surface loop are in close contact with the DNA. These data provide a template for the design of specifically targeted therapeutics for poor prognosis MLL-associated leukaemias.

About this StructureAbout this Structure

2J2S is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase., Allen MD, Grummitt CG, Hilcenko C, Min SY, Tonkin LM, Johnson CM, Freund SM, Bycroft M, Warren AJ, EMBO J. 2006 Oct 4;25(19):4503-12. Epub 2006 Sep 21. PMID:16990798 Page seeded by OCA on Sun May 4 08:15:37 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:2j2s.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 2j2s |SIZE=350|CAPTION= <scene name='initialview01'>2j2s</scene>
+The line below this paragraph, containing "STRUCTURE_2j2s", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-|GENE=
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-|DOMAIN=
+{{STRUCTURE_2j2s|  PDB=2j2s  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2j2s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2j2s OCA], [http://www.ebi.ac.uk/pdbsum/2j2s PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2j2s RCSB]</span>
-}}
 '''SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BINDING CXXC DOMAIN OF THE LEUKAEMIA-ASSOCIATED MLL HISTONE METHYLTRANSFERASE'''
@@ Line 33: / Line 30: @@
 [[Category: Warren, A J.]]
 [[Category: Young-Min, S.]]
-[[Category: alternative splicing]]
+[[Category: Alternative splicing]]
-[[Category: bromodomain]]
+[[Category: Bromodomain]]
-[[Category: chromatin]]
+[[Category: Chromatin]]
-[[Category: chromosomal rearrangement]]
+[[Category: Chromosomal rearrangement]]
-[[Category: cpg dinucleotide]]
+[[Category: Cpg dinucleotide]]
-[[Category: cxxc]]
+[[Category: Cxxc]]
-[[Category: dna-binding]]
+[[Category: Dna-binding]]
-[[Category: hox gene]]
+[[Category: Hox gene]]
-[[Category: mbd1]]
+[[Category: Mbd1]]
-[[Category: metal-binding]]
+[[Category: Metal-binding]]
-[[Category: methylation]]
+[[Category: Methylation]]
-[[Category: mixed lineage leukaemia]]
+[[Category: Mixed lineage leukaemia]]
-[[Category: nuclear protein]]
+[[Category: Nuclear protein]]
-[[Category: phosphorylation]]
+[[Category: Phosphorylation]]
-[[Category: polymorphism]]
+[[Category: Polymorphism]]
-[[Category: proto-oncogene]]
+[[Category: Proto-oncogene]]
-[[Category: transcription]]
+[[Category: Transcription]]
-[[Category: transcription regulation]]
+[[Category: Transcription regulation]]
-[[Category: zinc]]
+[[Category: Zinc]]
-[[Category: zinc binding]]
+[[Category: Zinc binding]]
-[[Category: zinc-finger]]
+[[Category: Zinc-finger]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May  4 08:15:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:52:09 2008''