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Filling and mining the reactive metabolite target protein database
Robert P Hanzlik1, Jianwen Fang, Yakov M Koen
1Department of Medicinal Chemistry and Bioinformatics Core Facility, University of Kansas, Lawrence, 66045-7582, USA. rhanzlik@ku.edu
Chemico-Biological Interactions
|October 1, 2008
Summary
Cellular proteins can be modified by reactive metabolites, leading to cell death. The Reactive Metabolite Target Protein Database (TPDB) catalogs these protein targets to understand toxic mechanisms.
Area of Science:
- Biochemistry
- Toxicology
- Proteomics
Background:
- Protein post-translational modifications regulate endogenous protein function.
- Xenobiotic agents and their metabolites can modify cellular proteins, sometimes causing cytotoxicity.
- Understanding these modifications is crucial for toxicology and drug development.
Purpose of the Study:
- To characterize the Reactive Metabolite Target Protein Database (TPDB).
- To review the origins of information within the TPDB.
- To compare TPDB data with other toxicological '-omics' studies.
Main Methods:
- Database compilation and characterization.
- Literature review for identifying reactive metabolite-protein interactions.
- Comparative analysis with toxicogenomics and proteomics data.
- Bioinformatic analysis of target proteins.
Main Results:
- The TPDB provides a comprehensive, up-to-date listing of known reactive metabolite target proteins.
- Information in the TPDB originates from various experimental and observational studies.
- Comparison reveals unique insights from TPDB data relative to other '-omics' approaches.
- Bioinformatic analysis of target proteins can elucidate cytotoxic mechanisms.
Conclusions:
- The TPDB is a valuable resource for understanding xenobiotic-induced protein modifications.
- Integrating TPDB data with other '-omics' can advance toxicological research.
- Bioinformatic approaches using TPDB data aid in elucidating mechanisms of reactive metabolite toxicity.
