Interdomain interactions rearrangements control the reaction steps of a thermostable DNA alkyltransferase
Morrone C, Miggiano R, Serpe M, Massarotti A, Valenti A, Del Monaco G, Rossi M, Rossi F, Rizzi M, Perugino G, Ciaramella M
Biochimica et biophysica acta 1861: 86-96. (2017)
Alkylated DNA-protein alkyltransferases (AGTs) are conserved proteins that repair alkylation damage in DNA by using a single-step mechanism leading to irreversible alkylation of the catalytic cysteine in the active site. Trans-alkylation induces inactivation and destabilization of the protein, both in vitro and in vivo, likely triggering conformational changes. A complete picture of structural rearrangements occurring during the reaction cycle is missing, despite considerable interest raised by the peculiarity of AGT reaction, and the contribution of a functional AGT in limiting the efficacy of chemotherapy with alkylating drugs.