RGD Reference Report - Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. - Rat Genome Database

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

Authors: Min, J  Feng, Q  Li, Z  Zhang, Y  Xu, RM 
Citation: Min J, etal., Cell 2003 Mar 7;112(5):711-23.
RGD ID: 1359080
Pubmed: PMID:12628190   (View Abstract at PubMed)

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.



Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
DOT1LHumanhomocysteine metabolic pathway   NAS  RGD 
Dot1lRathomocysteine metabolic pathway   ISODOT1L (Homo sapiens) RGD 
DOT1LHumanmethionine cycle/metabolic pathway   TAS  RGD 
Dot1lRatmethionine cycle/metabolic pathway   ISODOT1L (Homo sapiens) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Dot1l  (DOT1 like histone lysine methyltransferase)

Genes (Homo sapiens)
DOT1L  (DOT1 like histone lysine methyltransferase)


Additional Information