Selenolysine in the Chemical Protein Synthesis of SUMOylated Glucokinase

Glucokinase (GK) controls the levels of glucose in the human body by catalyzing the phosphorylation of glucose during glycolysis. Recently, the small ubiquitin-like modifier (SUMO) was implicated in GK regulation as one of its post-translationally modifying proteins. Because of difficulties isolating SUMOylated GK biologically, an in-depth study of SUMO’s influence on GK function has not yet been performed.

The main challenge in this synthesis is the traceless isopeptide ligation of SUMO to GK. We have designed a selenolysine with selenol at the γ-position of the side chain to allow native chemical ligation of GK to SUMO, followed by selective deselenization to leave all native Cys residues in the protein untouched. Using chemical protein synthesis, we intend to obtain milligram-level quantities of SUMOylated GK for biological characterization.