Avicinylation (thioesterification): a protein modification that can regulate the response to oxidative and nitrosative stress.
Published
Journal Article
Avicins are a recently discovered family of plant-derived terpenoid molecules that possess proapoptotic, antiinflammatory, and cytoprotective properties in mammalian cells. Previous work demonstrating that avicins can exert their effects by suppressing or activating the redox-sensitive transcription factors NF-kappaB and nuclear factor-erythroid 2 p45-related factor (Nrf2), respectively, has raised the idea that they may react with critical cysteine residues. To understand the molecular mechanism through which avicins regulate protein function, we examined their effects on the paradigmatic redox-responsive transcriptional activator, OxyR of Escherichia coli, which protects bacterial cells against oxidative and nitrosative stresses. In vitro transcription assays demonstrated that avicins activate OxyR and its target genes katG and oxyS in a DTT-reversible manner. In addition, katG-dependent hydroperoxidase I activity was enhanced in avicin-treated bacteria. Mass spectrometric analysis of activated OxyR revealed thioesterification of the critical regulatory cysteine, Cys-199, to an avicin fragment comprising the outer monoterpene side chain. Our results indicate that avicinylation can induce adaptive responses that protect cells against oxidative or nitrosative stress. More generally, transesterification may represent a previously undescribed thiol-directed posttranslational modification, which extends the code for redox regulation of protein function.
Full Text
Duke Authors
Cited Authors
- Haridas, V; Kim, S-O; Nishimura, G; Hausladen, A; Stamler, JS; Gutterman, JU
Published Date
- July 19, 2005
Published In
Volume / Issue
- 102 / 29
Start / End Page
- 10088 - 10093
PubMed ID
- 16030151
Pubmed Central ID
- 16030151
International Standard Serial Number (ISSN)
- 0027-8424
Digital Object Identifier (DOI)
- 10.1073/pnas.0504430102
Language
- eng
Conference Location
- United States