Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase
作者： Joseph J Rasimas , Paula A Dalessio , Ira J Ropson , Anthony E Pegg , Michael G Fried
DOI: 10.1110/PS.03319404
关键词:
摘要: 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 rapidly ubiquitinated degraded. Here, we show that alkylation destabilizes native fold by 0.5–1.2 kcal/mole DNA-binding function 0.8–1.4 kcal/mole. On this basis, propose destabilization conformational ensemble acts as a signal for ubiquitination.
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