1NW3

Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase

1NW3 の概要

• エントリーDOI: 10.2210/pdb1nw3/pdb
• 分子名称: histone methyltransferase DOT1L, ACETATE ION, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: hdot1, histone lysine methyltransferase, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus: Q8TEK3
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 48155.76

構造登録者

Min, J.R.,Feng, Q.,Li, Z.H.,Zhang, Y.,Xu, R.M. (登録日: 2003-02-05, 公開日: 2003-03-25, 最終更新日: 2024-02-14)

主引用文献

Min, J.,Feng, Q.,Li, Z.,Zhang, Y.,Xu, R.M.
Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase
Cell(Cambridge,Mass.), 112:711-723, 2003

PubMed Abstract: Dot1 is an evolutionarily conserved histone methyltransferase that methylates lysine-79 of histone H3 in the core domain. Unlike other histone methyltransferases, Dot1 does not contain a SET domain, and it specifically methylates nucleosomal histone H3. We have solved a 2.5 A resolution structure of the catalytic domain of human Dot1, hDOT1L, in complex with S-adenosyl-L-methionine (SAM). The structure reveals a unique organization of a mainly alpha-helical N-terminal domain and a central open alpha/beta structure, an active site consisting of a SAM binding pocket, and a potential lysine binding channel. We also show that a flexible, positively charged region at the C terminus of the catalytic domain is critical for nucleosome binding and enzymatic activity. These structural and biochemical analyses, combined with molecular modeling, provide mechanistic insights into the catalytic mechanism and nucleosomal specificity of Dot1 proteins.

PubMed: 12628190
DOI: 10.1016/S0092-8674(03)00114-4

実験手法

X-RAY DIFFRACTION (2.5 Å)