CHED 796 |
| Protein methylation is a posttranslational modification that affects the spatial and temporal regulation of proteins. In particular, the action of protein lysine methyltransferases (PKMTs) is thought to contribute to important cellular processes such as gene expression and oncogene stability. Despite a burgeoning interest in lysine methylation, little is known with respect to the timing and localization of PKMT activity in vivo. Selective chemical probes have been used to elucidate the spatiotemporal features of many other proteins. However, finding such probes has been difficult for PKMTs because most share the highly conserved SET domain in their binding pocket. In order to circumvent this issue, we are using the so-called “bump-and-hole” approach to develop allele-specific inhibitors. Mutations are introduced into the conserved binding pocket by site-directed mutagenesis that can sensitize a specific PKMT to chemically-modified analogues of an inhibitor. In our studies, mutations of three active site residues (E356A, W352F, and H297K) were separately introduced into the SET-domain of SET7/9 by site-directed mutagenesis. The design of a specific enzyme/inhibitor pair should be applicable to other proteins containing a SET-domain and can give precise temporal and spatial information about their function in vivo. |
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Undergraduate Research Poster Session: Biochemistry
2:00 PM-4:00 PM, Monday, April 7, 2008 Morial Convention Center -- Hall A, Poster
Division of Chemical Education |