Catalytic DNA with phosphatase activity

Jagadeeswaran Chandrasekar, Scott K. Silverman

Research output: Contribution to journalArticle

Abstract

Catalytic DNA sequences (deoxyribozymes, DNA enzymes, or DNAzymes) have been identified by in vitro selection for various catalytic activities. Expanding the limits of DNA catalysis is an important fundamental objective and may facilitate practical utility of catalysts that can be obtained from entirely unbiased (random) sequence populations. In this study, we show that DNA can catalyze Zn2+-dependent phosphomonoester hydrolysis of tyrosine and serine side chains (i.e., exhibit phosphatase activity). The best deoxyribozyme decreases the half-life for phosphoserine hydrolysis from as high as >10 10 y to <1 h. The phosphatase activity also occurs with nonpeptidic substrates but with reduced efficiency, indicating a preference for phosphopeptides. The newly identified deoxyribozymes can function with multiple turnover using free peptide substrates, have activity in the presence of human cell lysate or BSA, and catalyze dephosphorylation of a larger protein substrate, suggesting broader application of DNA catalysts as artificial phosphatases.

Original languageEnglish (US)
Pages (from-to)5315-5320
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number14
DOIs
StatePublished - Apr 2 2013

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Catalytic DNA
Phosphoric Monoester Hydrolases
DNA
Hydrolysis
Phosphoserine
Phosphopeptides
Catalysis
Serine
Half-Life
Tyrosine
Peptides
Enzymes
Population
Proteins

ASJC Scopus subject areas

  • General

Cite this

Catalytic DNA with phosphatase activity. / Chandrasekar, Jagadeeswaran; Silverman, Scott K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 14, 02.04.2013, p. 5315-5320.

Research output: Contribution to journalArticle

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