6W8B
Structure of DNMT3A in complex with CGA DNA
6W8B の概要
エントリーDOI | 10.2210/pdb6w8b/pdb |
分子名称 | DNA (cytosine-5)-methyltransferase 3A, DNA (cytosine-5)-methyltransferase 3-like, CGA DNA (25-MER), ... (5 entities in total) |
機能のキーワード | dna methylation, dnmt3a, aml, epigenetics, transferase, transferase-dna complex, transferase/dna |
由来する生物種 | Homo sapiens (Human) 詳細 |
タンパク質・核酸の鎖数 | 12 |
化学式量合計 | 259851.22 |
構造登録者 | |
主引用文献 | Anteneh, H.,Fang, J.,Song, J. Structural basis for impairment of DNA methylation by the DNMT3A R882H mutation. Nat Commun, 11:2294-2294, 2020 Cited by PubMed Abstract: DNA methyltransferase DNMT3A is essential for establishment of mammalian DNA methylation during development. The R882H DNMT3A is a hotspot mutation in acute myeloid leukemia (AML) causing aberrant DNA methylation. However, how this mutation affects the structure and function of DNMT3A remains unclear. Here we report structural characterization of wild-type and R882H-mutated DNMT3A in complex with DNA substrates with different sequence contexts. A loop from the target recognition domain (TRD loop) recognizes the CpG dinucleotides in a +1 flanking site-dependent manner. The R882H mutation reduces the DNA binding at the homodimeric interface, as well as the molecular link between the homodimeric interface and TRD loop, leading to enhanced dynamics of TRD loop. Consistently, in vitro methylation analyses indicate that the R882H mutation compromises the enzymatic activity, CpG specificity and flanking sequence preference of DNMT3A. Together, this study uncovers multiple defects of DNMT3A caused by the R882H mutation in AML. PubMed: 32385248DOI: 10.1038/s41467-020-16213-9 主引用文献が同じPDBエントリー |
実験手法 | X-RAY DIFFRACTION (2.4 Å) |
構造検証レポート
検証レポート(詳細版)をダウンロード