PMID:10722679
| Citation |
Li, X, Wright, PM and Lu, AL (2000) The C-terminal domain of MutY glycosylase determines the 7,8-dihydro-8-oxo-guanine specificity and is crucial for mutation avoidance. J. Biol. Chem. 275:8448-55 |
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| Abstract |
Escherichia coli MutY is an adenine DNA glycosylase active on DNA substrates containing A/G, A/8-oxoG, or A/C mismatches and also has a weak guanine glycosylase activity on G/8-oxoG-containing DNA. The N-terminal domain of MutY, residues 1-226, has been shown to retain catalytic activity. Substrate binding, glycosylase, and Schiff base intermediate formation activities of the truncated and intact MutY were compared. MutY has high binding affinity with 8-oxoG when mispaired with A, G, T, C, or inosine. The truncated protein has more than 18-fold lower affinities for binding various 8-oxoG-containing mismatches when compared with intact MutY. MutY catalytic activity toward A/8-oxoG-containing DNA is much faster than that on A/G-containing DNA whereas deletion of the C-terminal domain reduces its catalytic preference for A/8-oxoG-DNA over A/G-DNA. MutY exerts more inhibition on the catalytic activity of MutM (Fpg) protein than does truncated MutY. The tight binding of MutY with GO mispaired with T, G, and apurinic/apyrimidinic sites may be involved in the regulation of MutM activity. An E. coli mutY strain that produces an N-terminal 249-residue truncated MutY confers a mutator phenotype. These findings strongly suggest that the C-terminal domain of MutY determines the 8-oxoG specificity and is crucial for mutation avoidance by oxidative damage. |
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| Keywords |
DNA Glycosylases; DNA Repair; DNA-Formamidopyrimidine Glycosylase; Escherichia coli Proteins; Guanosine/analogs & derivatives; Guanosine/metabolism; Models, Genetic; Mutagenesis; Mutation; N-Glycosyl Hydrolases/antagonists & inhibitors; N-Glycosyl Hydrolases/metabolism; Protein Structure, Tertiary; Sequence Deletion; Substrate Specificity |
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