CRYSTAL-STRUCTURE OF A SUICIDAL DNA-REPAIR PROTEIN - THE ADA O-6-METHYLGUANINE-DNA METHYLTRANSFERASE FROM ESCHERICHIA-COLI

The mutagenic and carcinogenic effects of simple alkylating agents are mainlydue to methylation at the O-6 position of guanine in DNA. O-6-m ethylguanine directs the incorporation of either thymine or cytosine w ithout blocking DNA replication, resulting in GC to AT transition muta tions. In prokaryotic and eukaryotic cells antimutagenic repair is eff ected by direct reversal of this DNA damage. A suicidal methyltransfer ase repair protein removesthe methyl group from DNA to one of its own cysteine residues. The resulting self-methylation of the active site c ysteine renders the protein inactive. Here we report the X-ray structu re of the 19 kDa C-terminal domain of the Escherichia coli ada gene pr oduct, the prototype of these suicidal methyltransferases. In the crys tal structure the active site cysteine is buried. We propose a model f or the significant conformational change that the protein must undergo inorder to bind DNA and effect methyl transfer.