Crystal Structure of Metallo DNA Duplex Containing Consecutive Watson–Crick‐like T–Hg^II–T Base Pairs

Abstract

The metallo DNA duplex containing mercury-mediated T-T base pairs is an attractive biomacromolecular nanomaterial which can be applied to nanodevices such as ion sensors. Reported herein is the first crystal structure of a B-form DNA duplex containing two consecutive T-Hg(II)-T base pairs. The Hg(II) ion occupies the center between two T residues. The N3-Hg(II) bond distance is 2.0 Å. The relatively short Hg(II)-Hg(II) distance (3.3 Å) observed in consecutive T-Hg(II)-T base pairs suggests that the metallophilic attraction could exist between them and may stabilize the B-form double helix. To support this, the DNA duplex is largely distorted and adopts an unusual nonhelical conformation in the absence of Hg(II). The structure of the metallo DNA duplex itself and the Hg(II)-induced structural switching from the nonhelical form to the B-form provide the basis for structure-based design of metal-conjugated nucleic acid nanomaterials.

Fluorescent Base Analogue Reveals T-HgII-T Base Pairs Have High Kinetic Stabilities That Perturb DNA Metabolism

“…30 Previous studies have demonstrated that T-Hg II -T base pairs exhibit similar thermal stabilities and structural features as T-A base pairs in duplex DNA. [10][11][12] The perception of analogous behavior of T-Hg The kinetic parameters of mercury binding reactions are expected to be highly relevant in vivo, where high concentrations of protein thiols and glutathione (20 -50 mM total) would be expected to easily out-compete DNA for Hg II binding. 31 Amazingly, the addition of micromolar concentrations of Hg II (5 µM) to living cells resulted in the formation of highstability DNA-Hg II adducts at a frequency of 0.3% of all base pairs.…”

On the importance of antiparallel C O⋯C–F interactions in N1-(3-hydroxypropyl)-5-fluorouracilate–Hg(II) complex: A combined X-ray and DFT study

“…In fact a review was recently published [36], however the number of X-ray structures is still limited [10]. To this respect, the structure of a duplex with the thymineHg-thymine (N(3)-Hg-N(3)) recognition pattern has been recently described [37], which is similar to the previously described for bis(1-methylthyminato)mercury(II) [34] complex. Moreover, the coordination of Hg(II) to O(4) atom has been described in a mercuric chloride complex with uracil and dihydrouracil [35].…”

Artificial DNA Base Pairing Mediated by Diverse Metal Ions

“…52 The structure of THg II T pairs inside DNA duplexes has recently been characterized by NMR spectroscopy 53 as well as X-ray crystallography. 54 As for RNA derivatives, the formation of Hg(II)-mediated uracil base pairs (UHg II U) was demonstrated within RNA duplexes. 55 Most recently, a fluorescent analogue of T has been reported that is a promising artificial nucleobase to study the formation of T Hg II T base pairs by fluorescence spectroscopy.…”