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

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.

authors

Bai H,Kath JE,Zörgiebel FM,Sun M,Ghosh P,Hatfull GF,Grindley ND,Marko JF

doi

10.1073/pnas.1203118109

subject

Has Abstract

pub_date

2012-10-09 00:00:00

pages

16546-51

issue

41

eissn

0027-8424

issn

1091-6490

pii

1203118109

journal_volume

109

pub_type

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