Harnessing proteasome dynamics and allostery in drug design.

ABSTRACT:

Significance

The proteasome is the essential protease that is responsible for regulated cleavage of the bulk of intracellular proteins. Its central role in cellular physiology has been exploited in therapies against aggressive cancers where proteasome-specific competitive inhibitors that block proteasome active centers are very effectively used. However, drugs regulating this essential protease are likely to have broader clinical usefulness. The non-catalytic sites of the proteasome emerge as an attractive alternative target in search of highly specific and diverse proteasome regulators.

Recent advances

Crystallographic models of the proteasome leave the false impression of fixed structures with minimal molecular dynamics lacking long-distance allosteric signaling. However,

SUBMITTER: Gaczynska M 

PROVIDER: S-EPMC4241894 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature