Min, J. R., Feng, Q., Li, Z. Z., Zhang, Y., Xu, R. M. (March 2003) Structure of the catalytic domain of human DOT1L, a Non-SET domain nucleosomal histone methyltransferase. Cell, 112 (5). pp. 711-723. ISSN 0092-8674
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 Angstrom 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.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | CRYSTAL-STRUCTURE LYSINE METHYLTRANSFERASE SILENCING PROTEIN DIFFRACTION DATA CORE PARTICLE METHYLATION H3 CHROMATIN UBIQUITINATION YEAST |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation > histone methylation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein methylation |
| CSHL Authors: | |
| Communities: | CSHL labs > Xu lab |
| Depositing User: | Matt Covey |
| Date: | March 2003 |
| Date Deposited: | 01 Jul 2013 18:48 |
| Last Modified: | 01 Jul 2013 18:48 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/27900 |
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