Structural Biology of Human H3K9 Methyltransferases

• DOI: 10.1371/journal.pone.0008570
• Publication Date: 2010-01-09T00:16:13Z
• Authors: Hong Wu; Jinrong Min; Vladimir V. Lunin; Tatiana Antoshenko; Ludmila Dombrovski; Hong Zeng; Abdellah Allali-H...; Valérie Campagna-...; Masoud Vedadi; Cheryl H. Arrowsmith; Alexander N. Plot...; Matthieu Schapira
• Keywords: Docking (animal); Histone Methylation; Plug-in

SET domain methyltransferases deposit methyl marks on specific histone tail lysine residues and play a major role in epigenetic regulation of gene transcription. We solved the structures catalytic domains GLP, G9a, Suv39H2 PRDM2, four eight known human H3K9 their apo conformation or complex with donating cofactor, peptide substrates. analyzed structural determinants for methylation state specificity, designed G9a mutant able to tri-methylate H3K9. show that I-SET acts as rigid docking platform, while induced-fit Post-SET is necessary achieve catalytically competent conformation. also propose model where long-range electrostatics bring enzyme substrate together, presence an arginine upstream target critical binding specificity. Enhanced version This article can be viewed enhanced which text integrated interactive 3D representations animated transitions. Please note web plugin required access this functionality. Instructions installation use are available Text S1.