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N-terminal domain of Fpg (formamidopyrimidine-DNA glycosylase, MutM)_Nei (endonuclease VIII) base-excision repair DNA glycosylases DNA glycosylases maintain genome integrity by recognizing base lesions created by ionizing radiation, alkylating or oxidizing agents, and endogenous reactive oxygen species. These enzymes initiate the base-excision repair process, which is completed with the help of enzymes such as phosphodiesterases, AP endonucleases, DNA polymerases and DNA ligases. DNA glycolsylases cleave the N-glycosyl bond between the sugar and the damaged base, creating an AP (apurinic/apyrimidinic) site. The FpgNei DNA glycosylases represent one of the two structural superfamilies of DNA glycosylases that recognize oxidized bases (the other is the HTH-GPD superfamily exemplified by Escherichia coli Nth). Most FpgNei DNA glycosylases use their N-terminal proline residue as the key catalytic nucleophile, and the reaction proceeds via a Schiff base intermediate. One exception is mouse Nei-like glycosylase 3 (Neil3) which forms a Schiff base intermediate via its N-terminal valine. In addition to this FpgNei_N domain, FpgNei proteins have a helix-two-turn-helix (H2TH) domain and a zinc (or zincless)-finger motif which also contribute residues to the active site. FpgNei DNA glycosylases have a broad substrate specificity. They are bifunctional, in addition to the glycosylase (recognition) activity, they have a lyase (cleaving) activity on the phosphodiester backbone of the DNA at the AP site. This superfamily includes eukaryotic, bacterial, and viral proteins. |
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