Reactive Metabolite Target Protein Database (TPDB)

Abstract

The biotransformation of drugs and xenobiotic chemicals in living cells sometimes generates chemically reactive metabolites (CRMs) that diffuse through the cell and react covalently with cellular constituents, especially proteins. In some cases this covalent binding may impair the function of the protein(s) leading to cellular injury and even cell death. The elucidation of the chemistry involved in the bioactivation, the details of the ensuing protein modification, and the connection between protein binding and toxicity, became a major pursuit in a number of laboratories starting in the early 1970s. An attempt to collect all the relevant data about the proteins targeted by CRMs led to the construction of the Reactive Metabolite Target Protein Database (TPDB) at the University of Kansas. This curated, searchable database became freely available online in January 2006, and was maintained until July 2020, when its maintenance ceased. This Narrative describes the nature and extent of the data that was compiled and the searches that could be implemented within the TPDB. The results of analyses of that data have been published elsewhere. All of the data originally compiled, including a list of all pertinent literature references, is now available in the Narrative and the associated Appendices at http://hdl.handle.net/1808/30592.

List of Appendices:

1. Home page.pdf

2. Help page.pdf

3. Distribution of studies.xlsx

4. Chemical structures and abbreviations.pdf

5. List of hits and proteins.xlsx

6. List of protein "orthologs" (≥90% similar).xlsx

7. Commonality matrix, orthologs excluded.xlsx

8. Commonality matrix, orthologs included.xlsx

9. Targets proteins ranked by hit frequency.xlsx

10. Chemicals ranked by number of targets.xlsx

11. References cited in TPDB.xlsx