3d29
From Proteopedia
Proteasome Inhibition by Fellutamide B
Overview
Neurotrophic small molecules have the potential to aid in the treatment of neuronal injury and neurodegenerative diseases. The natural product fellutamide B, originally isolated from Penicillium fellutanum, potently induces nerve growth factor (NGF) release from fibroblasts and glial-derived cells, although the mechanism for this neurotrophic activity has not been elucidated. Here, we report that fellutamide B potently inhibits proteasome catalytic activity. High-resolution structural information obtained from cocrystallization of the 20S proteasome reveals novel aspects regarding beta-subunit binding and adduct formation by fellutamide B to inhibit their hydrolytic activity. We demonstrate that fellutamide B and other proteasome inhibitors increased NGF gene transcription via a cis-acting element (or elements) in the promoter. These results demonstrate an unrecognized connection between proteasome inhibition and NGF production, suggesting a possible new strategy in the development of neurotrophic agents.
About this Structure
3D29 is a Protein complex structure of sequences from Saccharomyces cerevisiae. Full crystallographic information is available from OCA.
Reference
Proteasome inhibition by fellutamide B induces nerve growth factor synthesis., Hines J, Groll M, Fahnestock M, Crews CM, Chem Biol. 2008 May;15(5):501-12. PMID:18482702 Page seeded by OCA on Wed Jun 11 10:51:15 2008
Categories: Proteasome endopeptidase complex | Protein complex | Saccharomyces cerevisiae | Crews, M C. | Fahnestock, M. | Groll, M. | Hines, J. | Anti-parallel beta-sheet structure flanked by alpha-helice | Cytoplasm | Hydrolase | Nucleus | Phosphoprotein | Protease | Proteasome | Threonine protease | Ubl conjugation | Zymogen
