Covalent Inhibition of the Human 20S Proteasome with Homobelactosin C Inquired by QM/MM Studies.

ABSTRACT: 20S proteasome is a main player in the protein degradation pathway in the cytosol, thus intervening in multiple pivotal cellular processes. Over the years the proteasome has emerged as a crucial target for the treatment of many diseases such as neurodegenerative diseases, cancer, autoimmune diseases, developmental disorders, cystic fibrosis, diabetes, cardiac diseases, atherosclerosis, and aging. In this work, the mechanism of proteasome covalent inhibition with bisbenzyl-protected homobelactosin C (hBelC) was explored using quantum mechanics/molecular mechanics (QM/MM) methods. Molecular dynamic simulations were used to describe key interactions established between the hBelC and its unique binding mode in the primed site of the β5 subunit. The free energy surfaces were computed to charact

SUBMITTER: Serrano-Aparicio N 

PROVIDER: S-EPMC9143130 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature