Structural Analysis of Metal Interactions with the Dinucleotide Duplex, dCG·dCG, Using Ion Mobility Mass Spectrometry (original) (raw)
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Interactions Between Metal Ions and DNA
Structure and Bonding, 2019
84 years elapsed between the announcements of the Periodic Table and that of the DNA double helix in 1953, and the two have been combined in many ways since then. In this chapter an outline of the fundamentals of DNA structure leads into a range of examples showing how the natural magnesium and potassium ions found in nature can be substituted in a diversity of applications. The dynamic structures found in nature have been studied in the more controlled, but artificial environment of the DNA crystal using examples from sodium to platinum, and also in a range of DNA-binding metal complexes. While nmr is an essential technique for studying nucleic acid structure and conformation, most of our knowledge of metal ion binding has come from X-ray crystallography. These days the structures studied, and therefore also the diversity of metal binding, go beyond the double helix to triplexes, hairpin loops, junctions and quadruplexes, and the chapter describes briefly how these pieces fit into the DNA jigsaw. In a final section, the roles of metal cations in the crystallisation of new DNA structures are discussed, along with an introduction to the versatility of the Periodic Table of absorption edges for nucleic acid structure determination.
Cations as hydrogen bond donors: A view of electrostatic interactions in DNA
2003
Cations are bound to nucleic acids in a solvated state. High-resolution X-ray diffraction studies of oligonucleotides provide a detailed view of Mg 2+ , and occasionally other ions bound to DNA. In a survey of several such structures, certain general observations emerge. First, cations bind preferentially to the guanine base in the major groove or to phosphate group oxygen atoms. Second, cations interact with DNA most frequently via water molecules in their primary solvation shell, direct ion-DNA contacts being only rarely observed. Thus, the solvated ions should be viewed as hydrogen bond donors in addition to point charges. Finally, ion interaction sites are readily exchangeable: The same site may be occupied by any ion, including spermine, as well as by a water molecule.
Journal of Inorganic Biochemistry, 1995
Trace amounts of metals are found in nucleic acids isolated from a wide range of biological materials [1]. The important roles of metal ions in the natural processes involving nucleic acids and their constituents have been realised during the last decades. The metal ions may interact non-covalently as counter ions to balance the negative charge of the phosphate backbone and/or establish strong covalent bonds with specific ligand sites on the nucleobases. In our NMR studies on the metal ion binding to a series of different double helical oligonucleotides we have found evidence of sequence-selective binding [2, 3]. In the present work we have investigated the interaction between cobalt(ll) ions and the double helical duplex [d(ATGGGTACCCAT] 2 by means of 1D and 2D proton NMR spectroscopy. This sequence has earlier been shown to interact selectively with Zn(ll) ions [4]. Cobalt(ll) is expected to bind to oligonucleotides both at the nucleobases and at the phosphate groups. Preliminary 1D NMR spectra indicate that Co(ll) ions do not induce strand separation and furthermore, that the duplex remain in the right-handed B-DNA form.
Biochemistry, 1998
The potassium form of d(CGCGAATTCGCG) solved by X-ray diffraction to 1.75 Å resolution indicates that monovalent cations penetrate the primary and secondary layers of the "spine of hydration". Both the sodium [Shui, X., McFail-Isom, L., Hu, G. G., and Williams, L. D. (1998) Biochemistry 37, 8341-8355] and the potassium forms of the dodecamer at high resolution indicate that the original description of the spine, only two layers deep and with full occupancy by water molecules, requires substantive revision. The spine is merely the bottom two layers of a four layer solvent structure. The four layers combine to form a repeating motif of fused hexagons. The top two solvent layers were not apparent from previous medium-resolution diffraction data. We propose that the narrow minor groove and axial curvature of A-tract DNA arise from localization of cations within the minor groove. In general, the results described here support a model in which most or all forces that drive DNA away from canonical B-conformation are extrinsic and arise from interaction of DNA with its environment. Intrinsic forces, originating from direct base-base interactions such as stacking, hydrogen bonding, and steric repulsion among exocyclic groups appear to be insignificant. The time-averaged positions of the ubiquitous inorganic cations that surround DNA are influenced by DNA bases. The distribution of cations depends on sequence. Regions of high and low cation density are generated spontaneously in the solvent region by heterogeneous sequence or even within the grooves of homopolymers. The regions of high and low cation density deform DNA by electrostatic collapse. Thus, the effects of small inorganic cations on DNA structure are similar to the effects of proteins. RPG-95-116-03-GMC). ‡ Atomic coordinates and structure factors have been deposited in the NDB (sodium form entry code BDL084; potassium form entry code BD0005) and PDB.
Journal of Inorganic Biochemistry, 1994
The propensity of a large number of metal ions to induce cooperative conformational or structural transitions in double-stranded poly d(G-C) was assessed primarily by UV and CD spectrometry. This ability was seen to be an intrinsic property of most metal ions. The observed (metal ion)/(polydeoxynucleotide) mole ratio calculated per G-C base pair and corresponding to the midpoints of the principal transition ranged from 0.3 (Ag(IIl) to 100 (Al(II1)). A strong correlation was seen [y =-l.Ol(log XI + 3.26, r = 0.95, n = 201 between the (metal ion)/(poly d(G-C)) mole ratio required for the transition midpoint (x) and a covalent index to complex stability (y) of the metal ions. This relationship was independent of the types of transitions observed (monophasic or biphasic) or of specific conformations (e.g., B, Z, @>. The y index measures the ability of metal ions to bind to nitrogen and/or sulphur donor atoms in ligands compared to oxygen centers; equilibrium analysis indicates that the mole-ratio x decreases with increasing affinity of metal ions for poly d(G-C). Thus the observed relationship suggests that base-nitrogen binding facilitates the induced transitions. In general, metal ions designated as Class B or nitrogen/sulphur seeking (AgtI), Hg(II), and Ru(III)) induced monophasic transitions, whereas Class A or oxygen seeking ions (La(III1, Ce(III), Tb(III), Dy(III)) induced biphasic transitions. Transitions generated by ions of more ambivalent ligand preference (Borderline ions) were either monophasic (M&I), Fe(III), Cu(II), Cd(B), In(III), and Pb(I1)) or biphasic (Cr(III), Co(B), Ni(I1) and Zn(I1)). Poorly defined transition-curve profiles were observed for Pt(II), Pd(II), and Al~III). Specific conformational assignments were made for some of the observed transitions. For a limited number of metal ions (NXII), Cu(II), Cd(B), Ag(I), Hg(II)), interaction with calf thymus DNA was similarly examined. In these instances, the susceptibility to DNase 1 digestion of both the DNA and polydeoxynucleotide complexes was assessed.
Stability and electronic structure ofM-DNA: Role of metal position
Physical Review B, 2011
We investigate, by first-principles density-functional calculations, fragments and periodic helices of CG-and AT-DNA, modified by incorporation of Zn 2+ cations. We study the relative stability of different binding sites for the metal ions as well as different methods of charge neutralization. We find that binding the Zn cation to the N(7) atom of guanine or adenine leads always to lower energies than substitution of an imino proton between two H-bonded bases. Also, neutralizing with OH − groups bonded to Zn 2+ is more stable than removing protons from the phosphate groups. Contrarily to common wisdom, we find that planarity of the base pairs is not an essential factor of stability, and that nonplanar base pairs can also be stacked effectively. Finally, we find that the most stable CG and AT helices, with Zn 2+ bonded to N(7) atoms and neutralized by OH − ions, have wide band gaps of more than 2 eV, and we conclude that they are poor candidates for electronic conduction.
Effect of Alkali Metal Cations on Length and Strength of Hydrogen Bonds in DNA Base Pairs
ChemPhysChem, 2020
For many years non-covalently bonded complexes of nucleobases have attracted considerable interest. However, there is a lack of information about the nature of hydrogen bonding between nucleobases when the bonding is affected by metal coordination to one of the nucleobases, and how the individual hydrogen bonds and aromaticity of nucleobases respond to the presence of the metal cation. Here we report a DFT computational study of nucleobase pairs interacting with alkali metal cations. The metal cations contribute to the stabilization of the base pairs to varying degrees depending on their position. The energy decomposition analysis revealed that the nature of bonding between nucleobases does not change much upon metal coordination. The effect of the cations on individual hydrogen bonds were described by changes in VDD charges on frontier atoms, H-bond length, bond energy from NBO analysis, and delocalization index from QTAIM calculations. The aromaticity changes were determined by HOMA index. 2 TOC Metal cations affects the hydrogen bonds in DNA base pairs. The strongest bond is b in AT pair, and a in GC pair. Interactions with the nitrogen atoms of adenine/guanine promotes the weakening of the strongest bonds, but interactions with the oxygen atoms of thymine/cytosine contribute to their further strengthening.
The Effects of Metal Ions on the Structure and Stability of the DNA Gyrase B Protein
Journal of Molecular Biology, 2005
The effects of mono-and divalent metal ions on the DNA gyrase B subunit, on its 43 kDa and 47 kDa domains, and on two mutants in the Toprim domain (D498A and D500C) were investigated by means of circular dichroism and protein melting experiments. Both types of metal ion, with the notable exception of Mn 2C , did not affect the conformational properties of the enzyme subunit at room temperature, but were able to produce selective and differential effects on protein stability. In particular, monovalent (K C ) ions increased the stability of the gyrase B structure, whereas destabilising effects were most prominent using Mn 2C as the metal ion. Ca 2C and Mg 2C produced comparable changes in the gyrase B melting profile. Additionally, we found that monovalent (K C ) ions were more effective in the 43 kDa N-terminal domain where ATP binding occurs, whereas divalent ions caused large modifications in the conformational stability of the 47 kDa C-terminal domain. Our results on gyrase B mutants indicate that D498 interacts with Mn 2C , whereas it has little effect on the binding of the other ions tested. A D500C mutation, in contrast, effectively impairs Mg 2C affinity, suggesting effective contacts between this ion and D500 in the wild-type enzyme. Hence, the sites of metal ion complexation within the Toprim domain are modulated by the nature of the ion species. These results suggest a double role played by metal ions in the catalytic steps involving DNA gyrase B. One has to do with direct involvement of cations complexed to the Toprim domain in the DNA cutting-rejoining process, the other, until now overlooked, is connected to the dramatic changes in protein flexibility produced by ion binding, which reduces the energy required for the huge conformational changes essential for the catalytic cycle to occur.