The inhibition mechanism of human 20 S proteasomes enables next-generation inhibitor design

Abstract

Insights into proteasome inhibition Proteasomes are large protein complexes that degrade and remove proteins to maintain proper cellular physiology and growth. Proteasomes are a validated target for anticancer therapy, but drug design has been hampered by poor understanding of how inhibitors interact with the active site. Schrader et al. succeeded in crystallizing various proteasome-inhibitor complexes. They subsequently obtained crystal structures for the native human proteasome and eight different inhibitor complexes at resolutions between 1.9 and 2.1 Å. The inhibitors sampled include drugs that are approved or in trial for cancer treatment. Science , this issue p. 594