title: Solution structure of the DNA methyl phosphotriester repair domain of Escherichia coli Ada.
abstract: The Escherichia coli Ada protein repairs methyl phosphotriesters in DNA by direct, irreversible methyl transfer to one of its own cysteine residues. The methyl-transfer process appears to be autocatalyzed by coordination of the acceptor residue, Cys-69, to a tightly bound zinc ion. Upon methyl transfer, Ada acquires the ability to bind DNA sequence-specifically and thereby to induce genes that confer resistance to methylating agents. The solution structure of an N-terminal 10-kDa fragment of Ada, which retains zinc binding and DNA methyl phosphotriester repair activities, was determined using multidimensional heteronuclear nuclear magnetic resonance techniques. The structure reveals a zinc-binding motif unlike any observed thus far in transcription factors or zinc-containing enzymes and provides insight into the mechanism of metalloactivated DNA repair.
authors.affiliation: Department of Chemistry, Harvard University, Cambridge, Massachusetts 02138.
authors.forename: L C
authors.initials: LC
authors.lastname: Myers
authors.forename: G L
authors.initials: GL
authors.lastname: Verdine
authors.forename: G
authors.initials: G
authors.lastname: Wagner
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000737:chemistry; D004926:Escherichia coli / Q000235:genetics; D029968:Escherichia coli Proteins; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D019853:O(6)-Methylguanine-DNA Methyltransferase; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions; D014157:Transcription Factors
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; D012996:Solutions; D014157:Transcription Factors; C045675:Ada protein, E coli; D019853:O(6)-Methylguanine-DNA Methyltransferase