1NW3

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

Summary for 1NW3

• Entry DOI: 10.2210/pdb1nw3/pdb
• Descriptor: histone methyltransferase DOT1L, ACETATE ION, SULFATE ION, ... (5 entities in total)
• Functional Keywords: hdot1, histone lysine methyltransferase, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q8TEK3
• Total number of polymer chains: 1
• Total formula weight: 48155.76

Authors

Min, J.R.,Feng, Q.,Li, Z.H.,Zhang, Y.,Xu, R.M. (deposition date: 2003-02-05, release date: 2003-03-25, Last modification date: 2024-02-14)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)