Function Assignments

Installation and function of N-terminal glyoxylyl and pyruvoyl groups in Secernin-3

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We are employing an in vitro biochemical approach to generate the electrophilic forms of SCRN proteins in both bacterial and mammalian host systems in order to identify the installation machinery, to understand the mechanisms of electrophile formation, and to characterize the activities of the electrophilic groups with respect to SCRN function. This project will be guided by our preliminary data that identifies a likely installation machinery. If, as predicted, the glyoxylyl moiety of SCRN3 is found to have a crucial role in an unpredicted catalytic activity of the protein, it would establish a shining example of the capacity of RP-ABPP to uncover entirely novel cofactors that cannot possibly be anticipated by sequence analysis and would almost certainly escape detection by untargeted proteomics.

Selected Publications

Matthews ML*, He L, Olson EJ, Horning BD, Correia BE, Yates JR, III, Dawson PE & Cravatt BF*. Chemoproteomic profiling and discovery of protein electrophiles in human cells Nat. Chem.  9, 234–243 (2017) [PDF]