Z DNA

The structure proposed by Watson and Crick was modeled to fit crystallographic data obtained on a sample of the most common form of DNA called B DNA Other forms include A DNA which is similar to but more compact than B DNA and Z DNA which IS a left handed double helix... 

By analogy to the levels of structure of proteins the primary structure of DNA IS the sequence of bases along the polynucleotide chain and the A DNA B DNA and Z DNA helices are varieties of secondary structures... 

Short segments of poly(dG—dC) incorporated within plasmids, or citcular DNA, adopt the Z-conformation under negative superhehcal stress. This left-handed DNA may be important in genetic control. On the other hand, the stmctural alteration of the helix requited in a B-to-Z transition within a plasmid is radical, and would involve either a multistep mechanism or the complete melting and reformation of helix. The improbability of such transitions has led to questions concerning the feasibility of a biological role for Z-DNA. 

Early diffraction photographs of such DNA fibers taken by Rosalind Franklin and Maurice Wilkins in London and interpreted by James Watson and Francis Crick in Cambridge revealed two types of DNA structures A-DNA and B-DNA. The B-DNA form is obtained when DNA is fully hydrated as it is in vivo. A-DNA is obtained under dehydrated nonphysiological conditions. Improvements in the methods for the chemical synthesis of DNA have recently made it possible to study crystals of short DNA molecules of any selected sequence. These studies have essentially confirmed the refined fiber diffraction models for A- and B-DNA and in addition have given details of small structural variations for different DNA sequences. Furthermore, a new structural form of DNA, called Z-DNA, has been discovered. 

Figure 7.2 Three helical forms of DNA, each containing 22 nucleotide pairs, shown in both side and top views. The sugar-phosphate backbone is dark the paired nucleotide bases are light, (a) B-DNA, which is the most common form in cells, (b) A-DNA, which is obtained under dehydrated nonphysiological conditions. Notice the hole along the helical axis in this form, (c) Z-DNA, which can be formed by certain DNA sequences under special circumstances. (Courtesy of Richard Feldmann.)...

The specific protein-DNA interactions described in this book are all with DNA in its regular B-form, or, in some cases with distorted B-DNA. In biological systems DNA appears not to adopt the A conformation, although double-stranded RNA does preferentially adopt this conformation in vivo. Whether or not Z-DNA occurs in nature is a matter of controversy. However, the formation of A-DNA and Z-DNA in vitro does illustrate the large structural changes that DNA can be forced to undergo. 

The DNA helix has major and minor grooves Z-DNA forms a zigzag pattern B-DNA is the preferred conformation in vivo Specific base sequences can be recognized in B-DNA Conclusion Selected readings... 

An alternative form of the right-handed double helix is A-DNA. A-DNA molecules differ in a number of ways from B-DNA. The pitch, or distance required to complete one helical turn, is different. In B-DNA, it is 3.4 nm, whereas in A-DNA it is 2.46 nm. One turn in A-DNA requires 11 bp to complete. Depending on local sequence, 10 to 10.6 bp define one helical turn in B-form DNA. In A-DNA, the base pairs are no longer nearly perpendicular to the helix axis but instead are tilted 19° with respect to this axis. Successive base pairs occur every 0.23 nm along the axis, as opposed to 0.332 nm in B-DNA. The B-form of DNA is thus longer and thinner than the short, squat A-form, which has its base pairs displaced around, rather than centered on, the helix axis. Figure 12.13 shows the relevant structural characteristics of the A- and B-forms of DNA. (Z-DNA, another form of DNA to be discussed shortly, is also depicted in Figure 12.13.) A comparison of the structural properties of A-, B-, and Z-DNA is summarized in Table 12.1. 

FIGURE 12.13 (here and on the facing page) Comparison of the A-, B-, and Z-forms of the DNA double helix. The distance required to complete one helical torn is shorter in A-DNA than it is in B-DNA. The alternating pyrimidine-pnrine sequence of Z-DNA is the... 

FIGURE 12.14 Comparison of the deoxy-guanosine conformation in B- and Z-DNA. In B-DNA, the Cl -N-9 glycosyl bond is always in the anti position (lefi). In contrast, in the left-handed Z-DNA structure, this bond rotates (as shown) to adopt the syn conformation. 

The Z-form can arise in sequences that are not strictly alternating Py-Pu. For example, the hexanucleotide " CGAT" CG, a Py-Pu-Pu-Py-Py-Pu sequence containing two 5-methylcytosines crystallizes as Z-DNA. Indeed, the in vivo... 

Rich, A., Nordheim, A., and Wang, A. H.-J., 1984. The chemi.stry and biology of left-handed Z-DNA. Annual Review of Biochemistry 53 791-846. 

There are therefore four adjustable parameters per atom in the refinement (xy, yy, Zj, By). In the computer experiments we have carried out to test the assumptions of the nucleic acid refinement model we have generated sets of observed structure factors F (Q), from the Z-DNA molecular dynamics trajectories. The thermal averaging implicit in Equation III.3 is accomplished by averaging the atomic structure factors obtained from coordinate sets sampled along the molecular dynamics trajectories at each temperature ... 

Parameters for refinement of simulation X-ray intensities of Z-DNA hexamer. First line before starting refinement second line after refinement with strong B restraints third line after refinement without B restraints... 

Figure 2. Temperature dependence of mean square atomic fluctuations of the Z-DNA hexamer. (a) Mean square atomic fluctuations were calculated directly from the molecular dynamics trajectories.

A good understanding of the properties of water is thus essential as we move to more complicated systems. We have been involving in the study of aqueous solution of many important biological molecules, such as acetylcholine, Gramicidin, deoxydinucleoside phosphate and proflavin, and DNA, etc., first at the Monte Carlo level and slowly moving to the molecular dynamics simulations. We will discuss some of the new results on the hydration structure and the dynamics of B- and Z-DNA in the presence of counterions in the following. 

The systems reported here are a single turn of B-DNA with G-C, A-T base pair sequence and the left handed Z-DNA with G-C base pair sequence. The B-DNA system is simulated for 4.0 psec and Z-DNA is simulated for 3.5 psec after equilibration. The simulation results are then analyzed for structural and dynamical properties. ... 

An analysis of the hydration structure of water molecules in the major and minor grooves in B-DNA has shown that there is a filament of water molecules connecting both the inter and the intra phosphate groups of the two strands of B-DNA. However, such a connectivity is absent in the case of Z-DNA confirming earlier MC simulation results. The probability density distributions of the counterions around DNA shows deep penetration of the counterions in Z-DNA compared to B-DNA. Further, these distributions suggest very limited mobility for the counterions and show well defined counter-ion pattern as originally suggested in the MC study. 

Zhang SG, Lockshin C, Herbert A et al (1992) Zuotin, a putative z-DNA binding- protein in saccharomyces-cerevisiae. EMBO J 11 3787-3796... 

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