Cover: DNA glycosylases of the helix-hairpin-helix superfamily act in base excision repair of a wide variety of DNA lesions. Mig.MthI of Methanobacterium thermoautotrophicum excises thymine and uracil from T/G and U/G mispairs, respectively. As shown by Fondufe-Mittendorf et al. in this issue [Nucleic Acids Res. (2002) 30, 614-621] the selectivity of this enzyme can be changed to that of MutY (removal of adenine from A/G mispairs) by replacing only two amino acid residues. From this, the mode of binding of a substrate thymine to Mig.MthI can be modelled as shown. A glutamic acid residue (top right) provides both base discrimination and catalysis via a bidentate hydrogen bridge. According to the model, leucine (top left) and alanine (bottom) are the only two amino residues in the shell immediately surrounding the substrate base that distinguish Mig.MthI from MutY.
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