1nw3 | pdb_00001nw3
Structure of the Catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase
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| 1nw3, resolution 2.5Å | |||||||||||||
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| Ligands: | ACT, SO4 and SAM | ||||||||||||
| Gene: | dot1 (Homo sapiens) | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Overview
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.
About this Structure
1NW3 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase., Min J, Feng Q, Li Z, Zhang Y, Xu RM, Cell. 2003 Mar 7;112(5):711-23. PMID:12628190
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