Remote control of DNA-acting enzymes by varying the Brownian dynamics of a distant DNA end

Hua Bai, James E. Kath, Felix Manuel Zörgiebel, Mingxuan Sun, Pallavi Ghosh, Graham F. Hatfull, Nigel D.F. Grindley, John F. Marko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Enzyme rates are usually considered to be dependent on local properties of the molecules involved in reactions. However, for large molecules, distant constraints might affect reaction rates by affecting dynamics leading to transition states. In single-molecule experiments we have found that enzymes that relax DNA torsional stress display rates that depend strongly on how the distant ends of the molecule are constrained; experiments with different-sized particles tethered to the end of 10-kb DNAs reveal enzyme rates inversely correlated with particle drag coefficients. This effect can be understood in terms of the coupling between molecule extension and local molecular stresses: The rate of bead thermal motion controls the rate at which transition states are visited in the middle of a long DNA. Importantly, we have also observed this effect for reactions on unsupercoiled DNA; other enzymes show rates unaffected by bead size. Our results reveal a unique mechanism through which enzyme rates can be controlled by constraints on macromolecular or supramolecular substrates.

Original languageEnglish (US)
Pages (from-to)16546-16551
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number41
DOIs
StatePublished - Oct 9 2012

Keywords

  • DNA topology
  • DNA-protein interactions
  • Enzyme kinetics
  • Molecular friction
  • Single-molecule biophysics

ASJC Scopus subject areas

  • General

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