A clamp-like biohybrid catalyst for DNA oxidation

Stijn F.M. Van Dongen, Joost Clerx, Kasper Nørgaard, Tom G. Bloemberg, Jeroen J.L.M. Cornelissen, Michael A. Trakselis, Scott W. Nelson, Stephen J. Benkovic, Alan E. Rowan, Roeland J.M. Nolte

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

In processive catalysis, a catalyst binds to a substrate and remains bound as it performs several consecutive reactions, as exemplified by DNA polymerases. Processivity is essential in nature and is often mediated by a clamp-like structure that physically tethers the catalyst to its (polymeric) template. In the case of the bacteriophage T4 replisome, a dedicated clamp protein acts as a processivity mediator by encircling DNA and subsequently recruiting its polymerase. Here we use this DNA-binding protein to construct a biohybrid catalyst. Conjugation of the clamp protein to a chemical catalyst with sequence-specific oxidation behaviour formed a catalytic clamp that can be loaded onto a DNA plasmid. The catalytic activity of the biohybrid catalyst was visualized using a procedure based on an atomic force microscopy method that detects and spatially locates oxidized sites in DNA. Varying the experimental conditions enabled switching between processive and distributive catalysis and influencing the sliding direction of this rotaxane-like catalyst.

Original languageEnglish (US)
Pages (from-to)945-951
Number of pages7
JournalNature Chemistry
Volume5
Issue number11
DOIs
StatePublished - Nov 1 2013

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Chemical Engineering(all)

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    Van Dongen, S. F. M., Clerx, J., Nørgaard, K., Bloemberg, T. G., Cornelissen, J. J. L. M., Trakselis, M. A., Nelson, S. W., Benkovic, S. J., Rowan, A. E., & Nolte, R. J. M. (2013). A clamp-like biohybrid catalyst for DNA oxidation. Nature Chemistry, 5(11), 945-951. https://doi.org/10.1038/nchem.1752