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| [[Image:3d29.jpg|left|200px]] | | {{Seed}} |
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| {{STRUCTURE_3d29| PDB=3d29 | SCENE= }} | | {{STRUCTURE_3d29| PDB=3d29 | SCENE= }} |
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| '''Proteasome Inhibition by Fellutamide B'''
| | ===Proteasome Inhibition by Fellutamide B=== |
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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_18482702}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 18482702 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_18482702}} |
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| ==About this Structure== | | ==About this Structure== |
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| [[Category: Ubl conjugation]] | | [[Category: Ubl conjugation]] |
| [[Category: Zymogen]] | | [[Category: Zymogen]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:51:15 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 13:55:52 2008'' |
