Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase

Joseph J. Rasimas, Paula A. Dalessio, Ira J. Ropson, Anthony E. Pegg, Michael G. Fried

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

O6-alkylguanine-DNA alkyltransferase (AGT) repairs pro-mutagenic O6-alkylguanine and O4-alkylthymine lesions in DNA. The alkylated form of the protein is not reactivated; instead, it is rapidly ubiquitinated and degraded. Here, we show that alkylation destabilizes the native fold of the protein by 0.5-1.2 kcal/mole and the DNA-binding function by 0.8-1.4 kcal/mole. On this basis, we propose that destabilization of the native conformational ensemble acts as a signal for ubiquitination.

Original languageEnglish (US)
Pages (from-to)301-305
Number of pages5
JournalProtein Science
Volume13
Issue number1
DOIs
StatePublished - Jan 2004

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Active-site alkylation destabilizes human O<sup>6</sup>-alkylguanine DNA alkyltransferase'. Together they form a unique fingerprint.

Cite this