Download MendeleyStructural basis for the excision repair of alkylation-damaged DNA.
Labahn, J., Scharer, O.D., Long, A., Ezaz-Nikpay, K., Verdine, G.L., Ellenberger, T.E.(1996) Cell 86: 321-329
- PubMed: 8706136
- DOI: https://doi.org/10.1016/s0092-8674(00)80103-8
- Primary Citation of Related Structures:
1MPG - PubMed Abstract:
Base-excision DNA repair proteins that target alkylation damage act on a variety of seemingly dissimilar adducts, yet fail to recognize other closely related lesions. The 1.8 A crystal structure of the monofunctional DNA glycosylase AlkA (E. coli 3-methyladenine-DNA glycosylase II) reveals a large hydrophobic cleft unusually rich in aromatic residues. An Asp residue projecting into this cleft is essential for catalysis, and it governs binding specificity for mechanism-based inhibitors. We propose that AlkA recognizes electron-deficient methylated bases through pi-donor/acceptor interactions involving the electron-rich aromatic cleft. Remarkably, AlkA is similar in fold and active site location to the bifunctional glycosylase/lyase endonuclease III, suggesting the two may employ fundamentally related mechanisms for base excision.
Organizational Affiliation:
Harvard Medical School, Department of Biological Chemistry and Molecular Pharmacology, Boston, Massachusetts02115, USA.
