Conformation in DNA

I.G., Lloyd, R.S., Prakash, S., and Prakash, L. (2005) Human DNA polymerase t promotes replication through a ring-closed minor-groove adduct that adopts a syn conformation in DNA. Mol. Cell Biol., 25, 8748-8754. 

Plavec J, Thibaudeau C, Viswanadham G, Sund C, Chattopadhyaya J (1994) How does the 3 -phosphate drive the sugar conformation in DNA J Chem Soc Chem Coirunun (1994) 781-783... 

A review on the information contained in sets of vicinal H- H coupling constants as evidence of furanose conformations in DNA has appeared." The relative strengths of the various gauche and anomeric effects which influence the pseudorotational equilibrium in the pentofiiianose moiety of nucleosides have been evaluated by an H-n.m.r. spectroscopic investigation of the abasic nucleoside equivalents 4."... 

Volkov, S.N. Conformational transitions and the mechanism of transmission of long-range effects in DNA. Preprint ITP-88-12E, Kiev (1988) 22 Krumhansl, J.A., Alexander, D.M. Nonlinear dynamics and conformational exitations in biomolecular materials. In Structure and dynamics nucleic acids and proteins. (Clementi, E., Sarma, R.H., eds) Adenine Press, New York (1983) 61-80... 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

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. 

Some of the procaryotic DNA-binding proteins are activated by the binding of an allosteric effector molecule. This event changes the conformation of the dimeric protein, causing the helix-tum-helix motifs to move so that they are 34 A apart and able to bind to the major groove. The dimeric repressor for purine biosynthesis, PurR, induces a sharp bend in DNA upon binding caused by insertion of a helices in the minor groove between the two... 

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... 

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. 

X-ray diffraction studies indicate the existence of a novel double-stranded DNA helical conformation in which AZ (the rise per base pair) = 0.32 nm and P (the pitch) = 3.36 nm. What are the other parameters of this novel helix (a) the number of base pairs per turn, (b) Abase pair), and (c) c (the true repeat) ... 

Greenall, R., Fuller, W. High Angle Fibre Diffraction Studies on Conformational Transitions in DNA Using Synchrotron Radiation. 151, 31-59 (1989). 

As has been demonstrated for tenofovir, when incorporated at the 3 -end of reverse transcriptase (RT)-driven DNA chain allows the PMPA residue to adopt multiple conformations [in contrast with the more rigid conformation of the 2, 3 -dideoxynucleosides (see infra) (Tuske et al. 2004). This greater flexibility in conformation may impede development of resistance to tenofovir. 

Coll, M., C. A. Erederick, A. H. J. Wang, and A. Rich. A bifurcated hydrogen-bonded conformation in the D(A-T) base-pairs of the DNA dodecamer D(CGCAAATTTGCG) and its complex with distamycin. Proc. Natl. Acad. Sci. USA 1987, 84, 8385-8389. 

Figure 39-15. The leucine zipper motif. A shows a helical wheel analysis of a carboxyl terminal portion of the DNA binding protein C/EBP. The amino acid sequence is displayed end-to-end down the axis of a schematic a-helix. The helical wheel consists of seven spokes that correspond to the seven amino acids that comprise every two turns of the a-helix. Note that leucine residues (L) occur at every seventh position. Other proteins with "leucine zippers" have a similar helical wheel pattern. B is a schematic model of the DNA binding domain of C/EBP. Two identical C/EBP polypeptide chains are held in dimer formation by the leucine zipper domain of each polypeptide (denoted by the rectangles and attached ovals). This association is apparently required to hold the DNA binding domains of each polypeptide (the shaded rectangles) in the proper conformation for DNA binding. (Courtesy ofS McKnight)...

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. 

Poly(dG-dC) poly(dG-dC) and its methylated analogue structures assume left-handed conformation (Z-DNA) in high molar sodium salt (Na", K" ), in low molar divalent cations (Ca", Mg", Ni ), micromolar concentrations of hexaamine cobalt chloride (Co(NH3)6)Cl3 and in millimolar concentrations of polyamines. In order to analyse the binding of berberine to Z-form DNA, Kumar et al. [186] reported that the Z-DNA structure of poly(dG-dC) poly(dG-dC) prepared in either a high salt concentration (4.0 M) or in 40 mM (Co(NH3)6)Cl3 remained invariant in the presence of berberine up to a nucleotide phosphate/alkaloid molar ratio of 0.8 and suggested that berberine neither bormd to Z-form DNA nor converted the Z-DNA to the... 

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