| First Author | Lau AY | Year | 1998 |
| Journal | Cell | Volume | 95 |
| Issue | 2 | Pages | 249-58 |
| PubMed ID | 9790531 | Mgi Jnum | J:50382 |
| Mgi Id | MGI:1303238 | Doi | 10.1016/s0092-8674(00)81755-9 |
| Citation | Lau AY, et al. (1998) Crystal structure of a human alkylbase-DNA repair enzyme complexed to DNA: mechanisms for nucleotide flipping and base excision. Cell 95(2):249-58 |
| abstractText | DNA N-glycosylases are base excision-repair proteins that locate and cleave damaged bases from DNA as the first step in restoring the genetic blueprint. The human enzyme 3-methyladenine DNA glycosylase removes a diverse group of damaged bases from DNA, including cytotoxic and mutagenic alkylation adducts of purines. We report the crystal structure of human 3-methyladenine DNA glycosylase complexed to a mechanism-based pyrrolidine inhibitor. The enzyme has intercalated into the minor groove of DNA, causing the abasic pyrrolidine nucleotide to flip into the enzyme active site, where a bound water is poised for nucleophilic attack. The structure shows an elegant means of exposing a nucleotide for base excision as well as a network of residues that could catalyze the in-line displacement of a damaged base from the phosphodeoxyribose backbone. |
