Journal:JBIC:29

High-resolution crystal structure of Z-DNA in complex with Cr3+ cations

Pawel Drozdzal, Miroslaw Gilski, Ryszard Kierzek, Lechoslaw Lomozik, Mariusz Jaskolski ^[1]

Molecular Tour
Trivalent chromium, a d³ cation, is poorly taken up by living cells. The Cr³⁺ ions are the final product of in vivo Cr⁶⁺ metabolism. However, Cr³⁺ in contrast to Cr⁶⁺ can form coordination complexes with macromolecules in the cells. In vitro biochemical experiments have shown that exposure of cells to Cr6+ yields binary (DNA–Cr³⁺) and ternary (DNA–Cr³⁺–ligand) adducts, DNA crosslinks, as well as oxidative DNA lesions. Despite the interest in DNA–Cr³⁺ interactions in biological systems, the existing literature provides detailed crystallographic structural data for only two, low-resolution DNA–Cr³⁺:DNA polymerase-β complexes, PDB 1zqe (3.7 Å) ֵand 1huz (2.6 ֵÅ).

Our work is part of our project aimed at characterizing metal-binding properties of left-handed Z-DNA helices. The three Cr3+ cations found in the asymmetric unit of the d(CGCGCG)₂–Cr³⁺ crystal structure do not form direct coordination bonds with either the guanine N/O atoms or the phosphate groups of the Z-DNA. Note the alternate conformations (I, green; II, orange) along the DNA chains. Click here to see the animation of this scene. Cr³⁺ cations shown as purple spheres. Instead, only water-mediated contacts between the nucleic acid and the Cr³⁺ cations are observed. The coordination spheres of Cr³⁺(1) and Cr³⁺(2) contain six water molecules each. The Cr³⁺(1) and Cr³⁺(2) ions are bridged by three water molecules from their coordination spheres, one of which (Wat1) is split into two sites. The hydration patterns of Cr³⁺(1) and Cr³⁺(2) are irregular and difficult to define (water molecules are represented by red spheres). The Cr³⁺(3) cation has distorted square pyramidal geometry.

We have used Z-DNA crystals to obtain accurate information about the geometrical parameters characterizing the coordination of Cr3+ ions by left-handed Z-DNA. The d(CGCGCG)2–Cr³⁺ structure is an excellent illustration of the flexibility of the Z-DNA molecule, visible in the adoption of multiple conformations (by the phosphate groups and the G2 nucleotide), in response to changes in its electrostatic and hydration environment, caused by the introduction of hydrated metal complexes.

PDB reference: High-resolution crystal structure of Z-DNA in complex with Cr3+ cations, 4r15.