@article{cf8c05ecacfe4129b25fd5896be7fc8e,
title = "Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase",
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.",
keywords = "DNA binding, Denaturation, O -methylguanine-methyltransferase, O-alkylguanine-DNA alkyltransferase, Protein-alkylation",
author = "Rasimas, \{Joseph J.\} and Dalessio, \{Paula A.\} and Ropson, \{Ira J.\} and Pegg, \{Anthony E.\} and Fried, \{Michael G.\}",
year = "2004",
month = jan,
doi = "10.1110/ps.03319404",
language = "English",
volume = "13",
pages = "301--305",
number = "1",
}