|
Etiology and Pathogenesis
> Tumorigenesis
|
|
J. Am. Chem. Soc.,128 (33), 10795 -10800,
2006. DOI: 10.1021/ja061795y, Web Release Date: 28 July 2006
|
|
|
|
|
Abstract |
|
|
|
Oxidative Damage to DNA: Counterion-Assisted
Addition of Water to Ionized DNA
Robert N. Barnett, Angelo
Bongiorno, Charles L. Cleveland, Abraham Joy, Uzi
Landman,* and Gary B. Schuster**
Contribution from the Schools of
Physics and Chemistry & Biochemistry, Georgia Institute of
Technology, Atlanta, Georgia 30332 -- *uzi.landman@physics.gatech.edu;
**gary.schuster@cos.gatech.edu -- Received March 15, 2006.
|
|
|
|
|
Oxidative damage to DNA, implicated in
mutagenesis, aging, and cancer, follows electron loss that generates a
radical cation that migrates to a guanine, where it may react with
water to form 8-oxo-7,8-dihydroguanine (8-OxoG).
Molecular dynamics and ab initio quantum simulations on a B-DNA
tetradecamer reveal activated reaction pathways that depend on the
local counterion arrangement.
The lowest activation barrier, 0.73 eV, is found for a reaction that
starts from a configuration where a Na+ resides in the
major groove near the N7 atoms of adjacent guanines, and evolves
through a transition state where a bond between a water oxygen atom
and a carbon atom forms concurrently with displacement of a proton
toward a neighboring water molecule.
Subsequently, a bonded complex of a hydronium ion and the nearest
backbone phosphate group forms.
This counterion-assisted proton shuttle mechanism is supported by
experiments exploiting selective substitution of backbone phosphates
by methylphosphonates.
|
|
|
|
|
Copyright © 2006 American Chemical
Society
|
|
|
Abstract
|
News
|
|
|
|
