Structural insights into Salinosporamide A mediated inhibition of the human 20S proteasome.

ABSTRACT: The 20S proteasome, a critical component of the ubiquitin-proteasome system, plays a central role in regulating protein degradation in eukaryotic cells. Marizomib (MZB), a natural γ-lactam-β-lactone compound derived from Salinispora tropica, is a potent 20S proteasome covalent inhibitor with demonstrated anticancer properties. Its broad-spectrum inhibition of all three proteasome subunits and ability to cross the blood-brain barrier has made it a promising therapeutic candidate for glioblastoma. Here, we present the cryo-EM structure of the human 20S proteasome in complex with MZB at 2.55 Å resolution. This structure reveals the binding mode of MZB to all six catalytic subunits within the two β-rings of the 20S proteasome, providing a detailed molecular understanding of its irrevers

SUBMITTER: Sulzen H 

PROVIDER: S-EPMC11838377 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature