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Nature. 1995 Jun 15;375(6532):611-4.

A DNA metalloenzyme with DNA ligase activity.

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  • 1Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.


Single-stranded DNA can fold into well-defined sequence-dependent tertiary structures that specifically bind a variety of target molecules, raising the possibility that some folded single-stranded DNAs might exhibit catalytic activities similar to those of ribozymes and protein enzymes. Derivatives of the hammerhead ribozyme that contain a majority of deoxyribonucleotides retain the ability to cleave RNA, and a 'deoxyribozyme' was generated by leaving all essential ribonucleotides of the hammerhead on the RNA 'substrate'. Recently in vitro selection has been used to isolate a DNA sequence that shows Pb(2+)-dependent RNA-cleaving activity. Here we report the isolation by in vitro selection of a small single-stranded DNA that is a Zn2+/Cu(2+)-dependent metalloenzyme. The enzyme catalyses the formation of a new phosphodiester bond by the condensation of the 5'-hydroxyl of one oligodeoxynucleotide and a 3'-phosphorimidazolide on another oligodeoxynucleotide, and shows multiple turnover ligation.

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