Antonio Astarita and Francesca Muzio

Abstract:

PRDM2 is a histone lysine methyltransferase important in cell division and differentiation that has been linked to human cancers. Conformational changes are hypothesized to be important for active site formation and enzyme activity. We aim to use fluorine-19 NMR (FNMR) spectroscopy to provide structural evidence for conformational changes in wild type PRDM2 and variants implicated in cancer. As a proof-of-principle, we have successfully expressed glutathione S-transferase (GST) in minimal media with fluorine-labeled indole derivatives, which are biosynthesized into the protein as fluorinated tryptophan residues. Structural studies of PRDM2 using FNMR to analyze changes in wild type and variant protein conformations with substrates could shed light on the general mechanism of action of PRDM2 and its role in human cancers.