Complex of G9a-like protein and BIX-01294, a small molecule inhibitor of G9a and G9a-like protein.
- First example of inhibitor bound enzymatic SET domain structure of a protein lysine methyltransferase.
- May show improved potency and selectivity of the G9a/GLP inhibitor.
Histone lysine methylation is an important regulator of gene expression and chromatin organization. The small molecule, BIX-01294 (a diazepin-quinazolin-amine derivative), inhibits G9a and G9a-like protein (GLP) histone lysine methyltransferases, which repress transcription by methylating histone H3 at lysine 9 (H3K9). It has been used in the generation of induced pluripotent stem cells. Here, the inhibitor is bound in the substrate peptide groove at the site where the histone H3 residues N-terminal to the target lysine would occupy and resembles the bound confirmation of histone H3 lysine 4 to arginine 8.
Complex available for licensing.
Publication: Chang et al. Nat Struct Mol Biol. 16:312-317. (2009)