2j2s

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(New page: 200px<br /> <applet load="2j2s" size="450" color="white" frame="true" align="right" spinBox="true" caption="2j2s" /> '''SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BIN...)
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'''SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BINDING CXXC DOMAIN OF THE LEUKAEMIA-ASSOCIATED MLL HISTONE METHYLTRANSFERASE'''<br />
'''SOLUTION STRUCTURE OF THE NONMETHYL-CPG-BINDING CXXC DOMAIN OF THE LEUKAEMIA-ASSOCIATED MLL HISTONE METHYLTRANSFERASE'''<br />
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==About this Structure==
==About this Structure==
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2J2S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2J2S OCA].
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2J2S is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2J2S OCA].
==Reference==
==Reference==
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[[Category: zinc-finger]]
[[Category: zinc-finger]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 22:51:09 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri Feb 15 17:37:02 2008''

Revision as of 15:37, 15 February 2008


2j2s

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

Contents

Overview

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.

Disease

Known diseases associated with this structure: Leukemia, myeloid/lymphoid or mixed-lineage OMIM:[159555]

About this Structure

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

Reference

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

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