Discussion

Abstract

In this work we have used the mathematical model for proteasome dynamics by Liepe et al. [1] to compare different proteasome isoforms and subtypes in terms of their transport- and active site-related parameters and have reported some major differences. In addition, we have incorporated inhibitor dynamics into this model and have used it to examine the influence of the different inhibitor-specific transport- and active site-related parameters on the inhibiting effect. Furthermore, we have shown how to modulate the inhibitor-specific transport parameters in order to obtain a very potent inhibitor and show that it is theoretically possible to design an inhibitor that is more specific for i-proteasome than s-proteasome, or vice versa, merely by selection of transport parameters.