Targeting Signals

Although Pex5p recognizes and binds both to SKL and KANL signals, its interactions with the SKL-tagged enzymes are far more robust. Since binding by Pex5p is the first step in the import of a given enzyme by the peroxisome, stronger binding affinities translate into substantially better import capabilities. These factors explain catalase’s poor interaction with Pex5p and subsequent reduced import capacity, particularly as the cell ages. In older cells, where import of all peroxisomal enzymes appears to be reduced, catalase with its weak PTS1, is the most dramatically affected. In fact, in aged cells catalase is at least partially mislocalized and in some cells, virtually no peroxisomal catalase is detected. When catalase is localized outside the peroxisome, it is far less effective at eliminating cellular hydrogen peroxide.

To reestablish the balance of pro-and antioxidants, EXT has engineered catalase to contain the high affinitybinding signal for Pex5p, namely SKL. EXT has already synthesized Catalase-SKL and developed a method to deliver the enzyme into human cells. Experimental results indicate that Catalase-SKL is both better recognized and bound by Pex5p and more efficiently imported into the peroxisome than the naturally occurring version. Correctly targeted Catalase-SKL also shows the critical ability to return hydrogen peroxide levels to normal in human cells.