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.
|Number of pages||5|
|State||Published - Jan 2004|
- DNA binding
- O -methylguanine-methyltransferase
- O-alkylguanine-DNA alkyltransferase
ASJC Scopus subject areas
- Molecular Biology