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

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.

journal_name

Cell

journal_title

Cell

authors

Min J,Feng Q,Li Z,Zhang Y,Xu RM

doi

10.1016/s0092-8674(03)00114-4

subject

Has Abstract

pub_date

2003-03-07 00:00:00

pages

711-23

issue

5

eissn

0092-8674

issn

1097-4172

pii

S0092867403001144

journal_volume

112

pub_type

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