The X-ray Structure determination of Alkylated DNA Base Excision Repair Enzymes

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Escherichia coli has two DNA repair enzymes that liberate 3-methyladenine from DNA damaged by carcinogenic and/or mutagenic alkylating agents, namely 3-methyladenine-DNA Glycosylases I and II.They are distinguishable by their molecular sizes, enzymic properties and responses to alkylating agents. An adaptive DNA repair enzyme, 3-methyladenine-DNA glycosylase II,catalyzes the release of several alkylated bases in addition to 3-methyladenine. We have determined the three-dimensional structure of 3-methyladenine-DNA glycosylase II at a 2.3* resolution. The enzyme consists of three domains, one alpha+beta fold domain and two all alpha-helical domains. The comparison of amino acid sequence with those of Bacillus subtilis and Saccharomyces cerevisiae 3-methyladenine-DNA glycosylases and mutagenic studies allow to propose that the active site is located in a cleft between domains II and III.On the other hand, a constitutive enzyme 3-methyladenine-DNA glycosylase I releases only 3-methyladenine. The crystallization of 3-methyladenine-DNA glycosylase I is in progress.