2j2s: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2j2s |SIZE=350|CAPTION= <scene name='initialview01'>2j2s</scene> | |PDB= 2j2s |SIZE=350|CAPTION= <scene name='initialview01'>2j2s</scene> | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ZN:ZINC ION'>ZN</scene> | |LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> | ||
|ACTIVITY= | |ACTIVITY= | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|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> | |||
}} | }} | ||
| Line 14: | Line 17: | ||
==Overview== | ==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. | 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 Structure== | ==About this Structure== | ||
| Line 33: | Line 33: | ||
[[Category: Warren, A J.]] | [[Category: Warren, A J.]] | ||
[[Category: Young-Min, S.]] | [[Category: Young-Min, S.]] | ||
[[Category: alternative splicing]] | [[Category: alternative splicing]] | ||
[[Category: bromodomain]] | [[Category: bromodomain]] | ||
| Line 56: | Line 55: | ||
[[Category: zinc-finger]] | [[Category: zinc-finger]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:52:09 2008'' | ||
Revision as of 03:52, 31 March 2008
| |||||||
| Ligands: | |||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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 Mon Mar 31 03:52:09 2008
Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)
OCA- Pages with broken file links
- Homo sapiens
- Single protein
- Allen, M D.
- Bycroft, M.
- Grummitt, C G.
- Hilcenko, C.
- Johnson, C M.
- Tonkin, L M.
- Warren, A J.
- Young-Min, S.
- Alternative splicing
- Bromodomain
- Chromatin
- Chromosomal rearrangement
- Cpg dinucleotide
- Cxxc
- Dna-binding
- Hox gene
- Mbd1
- Metal-binding
- Methylation
- Mixed lineage leukaemia
- Nuclear protein
- Phosphorylation
- Polymorphism
- Proto-oncogene
- Transcription
- Transcription regulation
- Zinc
- Zinc binding
- Zinc-finger