2J2S
Solution structure of the nonmethyl-CpG-binding CXXC domain of the leukaemia-associated MLL histone methyltransferase
Summary for 2J2S
| Entry DOI | 10.2210/pdb2j2s/pdb |
| Related | 2AGH |
| Descriptor | ZINC FINGER PROTEIN HRX, ZINC ION (2 entities in total) |
| Functional Keywords | transcription regulation, chromosomal rearrangement, zinc-finger, dna-binding, bromodomain, polymorphism, mixed lineage leukaemia, zinc binding, transcription, metal-binding, zinc, cxxc, mbd1, hox genes, chromatin, methylation, proto-oncogene, nuclear protein, phosphorylation, cpg dinucleotide, alternative splicing |
| Biological source | HOMO SAPIENS (HUMAN) |
| Cellular location | Nucleus . MLL cleavage product N320: Nucleus. MLL cleavage product C180: Nucleus: Q03164 |
| Total number of polymer chains | 1 |
| Total formula weight | 8197.48 |
| Authors | Allen, M.D.,Grummitt, C.G.,Hilcenko, C.,Young-Min, S.,Tonkin, L.M.,Johnson, C.M.,Bycroft, M.,Warren, A.J. (deposition date: 2006-08-17, release date: 2006-08-21, Last modification date: 2024-05-15) |
| Primary citation | Allen, M.D.,Grummitt, C.G.,Hilcenko, C.,Min, S.Y.,Tonkin, L.M.,Johnson, C.M.,Freund, S.M.,Bycroft, M.,Warren, A.J. Solution Structure of the Nonmethyl-Cpg-Binding Cxxc Domain of the Leukaemia-Associated Mll Histone Methyltransferase Embo J., 25:4503-, 2006 Cited by PubMed Abstract: 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. PubMed: 16990798DOI: 10.1038/SJ.EMBOJ.7601340 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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