Lack of proteasome active site allostery as revealed by subunit-specific inhibitors
Article
Myung, J, Kim, KB, Lindsten, K et al. (2001). Lack of proteasome active site allostery as revealed by subunit-specific inhibitors
. 7(2), 411-420. 10.1016/S1097-2765(01)00188-5
Myung, J, Kim, KB, Lindsten, K et al. (2001). Lack of proteasome active site allostery as revealed by subunit-specific inhibitors
. 7(2), 411-420. 10.1016/S1097-2765(01)00188-5
The chymotrypsin-like (CT-L) activity of the proteasome is downregulated by substrates of the peptidyl-glutamyl peptide hydrolyzing (PGPH) activity. To investigate the nature of such interactions, we synthesized selective α′,β′-epoxyketone inhibitors of the PGPH activity. In cellular proliferation and protein degradation assays, these inhibitors revealed that selective PGPH inhibition was insufficient to inhibit protein degradation, indicating that the CT-L and PGPH sites function independently. We also demonstrated that CT-L inhibition by a PGPH substrate does not require the occupancy of the PGPH site or hydrolysis of the PGPH substrate. Thus, these results support a model in which a substrate of one subunit regulates the activity of another via binding to a noncatalytic site(s) rather than through binding to an active site.
