B—> Z conformational transition

Binding [ (dien)PtC ]Cjl to poly(dG-dC) poly(dG-dC) Facilitates the B->Z Conformational Transition... 

Column 2 Methods used to assess the B-Z conformational transition. 

Vibrational spectroscopy and, in particular, Raman scattering have been used to elucidate selected interactions of DNAs. The B Z conformational transition of oligo-DNA duplexes and the interaction of the intercalating dye AO with calf thymus DNA have been explicitly analyzed in the preceding sections. 

SDEL was also used to study the coil-helix transition of an alanine-rich peptide [68], the conformational transition of sugar puckering in deoxyadenosine [69], polymerase P [70], and the B-Z DNA transition [71,72]. The coil to helix study [68] demonstrated several properties of SDEL trajectories, like the filtering of high frequency modes and the preservation of thermodynamic properties from slow degrees of freedom when the trajectory resolution is decreased. 

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. 

According to these transition state models2,. (y -products are formed via a chair (C) conformation where both the enolate and the imine are in E geometry (E,E) or via a boat (B) transition state where the enolate is in Z and the imine in Econfiguration C(E.E) or B(Z,E). antt-Products are formed via B(E,E) and C(Z,E) transition states. The transition states leading to 1 and 2 are based upon the more stable E geometry of the imine. For cyclic imines a complementary set of transition states can be applied based on the Z geometry of the imine. 

Recent advances of the Seeman group led to the construction of a nanomechanical device from DNA [89]. In this molecular apparatus, the ion-dependent transition of B-DNA into the Z-conformation is used to alter the distance between two DNA DX domains attached to the switchable double helix. Atomic displacements of about 2-6 nm were attained. Ionic switching of nanoparticles by means of DNA supercoiling has also been reported [53]. Additional advances regarding the use of DNA is nanomechanical devices have been reported by Fritz et al., who showed that an array of cantilevers can be used to... 

Identification of proteins that bind to Z-DNA added one further step to the establishment of the presence of Z-DNA in vivo and its possible biological role. Herbert and Rich [22] demonstrated an in vitro assay system where one type of double-stranded RNA adenosine deaminase, called DRAD-binding Z-DNA. There are evidences that topoisomerase II from Drosophila, hiunan and calf thymus recognizes a number of DNA shapes, including Z-DNA [34,35]. Bloomfield and coworkers [36] have found that the condensation of plasmids is enhanced by Z-DNA conformation in d(CG)n repeats. The information related to B-Z transition [31], the effect of ligands on it [28,29] and X-ray crystal structure data [37,38] appear to suggest that the possible biological role of this polymorphic form of DNA will be soon established. 

A closed circular duplex DNA has a 90 base-pair segment of alternating G and C residues. Upon transfer to a solution containing a high salt concentration, this segment undergoes a transition from the B conformation to the Z conformation. 

Suppose one double helical turn of a superhelical DNA molecule changes from a B conformation to the Z conformation. Calculate the approximate changes in (1) the linking AL/c, (2) the writhe AWr, and (3) the twist A Tw of the DNA as a result of this transition. Show your calculations and explain your answers. For this problem assume that the B form of DNA has 10.4 bp per turn. Why is the B—> Z transition favored in naturally occurring supercoiled DNA ... 

Fig. 4.7-2 exhibits characteristic Raman lines of Z form helices. It shows the Raman spectra of right-handed (top row) and left-handed (bottom row) conformations of the three polymers poly d(G-C), poly d(A-C). poly d(G-T), poly d(A-T), and of an oligomer d(CACGTG). Particularly noticeable features of the bottom row spectra (Z conformation) are the characteristic sugar-backbone lines around 815 and 746 cm, as well as the purine line of the syn conformation around 622 cm . Other important spectral changes reflecting a B Z transition are the emergence of an intense dG line at 1320 cm, the. shift of a purine line (dA from 1375 to 1362 cm, dG from 1363 to 1354 cm ), and the appearance of a dC line at 1264 cm (see Table 4.7-1). 

Substitution within a short DNA duplex amenable to Z-form DNA of two contiguous L-nucleotides stabilised the left-handed Z-conformation. The l-nucleotides induced, at low salt concentration, a local left-handed conformation different from the existing Z-DNA, but which contributed to the lower energy required for B- to Z-transition. The role of the 3 -5 exonuclease activity of the tumour suppressor p53 protein has been examined by an in vitro assay in which ODNs were terminated with either p-D or P-l of ddAMP or 3 -thio-ddc (SddC). °° The affinity of the p53 protein was shown to be five-fold lower for P-l nucleotides. 

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