Helical conformation nucleotides

The phase problem and the problem of arbitration. Fibrous structures are usually made up of linear polymers with helical conformations. Direct or experimental solution of the X-ray phase problem is not usually possible. However, the extensive symmetry of helical molecules means that the molecular asymmetric unit is commonly a relatively small chemical unit such as one nucleotide. It is therefore not difficult to fabricate a preliminary model (which incidently provides an approximate solution to the phase problem) and then to refine this model to provide a "best" solution. This process, however, provides no assurance that the solution is unique. Other stereochemically plausible models may have to be considered. Fortunately, the linked-atom least-squares approach provides a very good framework for objective arbitration independent refinements of competing models can provide the best models of each kind the final values of n or its components (eqn. xxiv) provide measures of the acceptability of various models these measures of relative acceptability can be compared using standard statistical tests (4) and the decision made whether or not a particular model is significantly superior to any other. 

First, given the wide range of prebiotic nucleic acids, ribose-based polymers may be the most eminently suited for catalysis. Eschenmoser has pointed out, for example, that nucleic acids constructed from hexose nucleotides form inflexible ribbon structures,61 poorly suited for convoluting into the complex shapes that are required for catalysis (e.g., the backbone of the projected tertiary structure of the Tetrahymena self-splicing intron folds back on itself a number of times).62 Conversely, backbones composed of acyclic nucleotides may be too flexible to adopt stable secondary structures (since a great deal of entropy would necessarily be lost on freezing into a given conformer). Ribose, on the other hand, has a limited flexibility because of its pseudorotation cycle, and RNA can adopt a variety of helical conformations. 

DNA is a structurally polymorphic macromolecule which, depending on nucleotide sequence and environmental conditions, can adopt a variety of conformations. The double helical structure of DNA (dsDNA) consists of two strands, each of them on the outside of the double helix and formed by alternating phosphate and pentose groups in which phosphodiester bridges provide the covalent continuity. The two chains of the double helix are held... 

The conformation and helical sense of the structure interconnecting the metal-coordinated oxygens and the phosphorus atoms of the nucleotide. 

Fig. 5.19. GTP and GDP structures of transducin. The Ga,t subunit of transducin possesses—in contrast to Ras protein and to other small regulatory GTPases —an a-hehcal domain that hides and closes the G-nucleotide binding pocket. The conformational changes that accompany the transition from the inactive G t GDP form (a) into the active G t GTP form (b), are restricted to three structural sections that are known as switches I, II and III. Switch I includes the link of the a-helical domain with P2, switch II affects in particular hehx a2, and switch III, the pS—a3 loop. Switch III includes a sequence that is characteristic for the a-subunits of the heterotrimeric G-proteins. The conformational changes of switches II and III affect structural sections that are assumed to be binding sites for the effector molecule adenylyl cyclase (AC) and the y-subunit of cGMP-dependent phosphodiesterase (PDEy), based on mutation experiments and biochemical investigations. MOLSKRIPT representation according to Krauhs, (1991).

First identified in 1986 as the catalytic active element in the replication cycle of certain viruses, the hammerhead ribozymes (HHRz) are the smallest known, naturally occurring RNA endonucleases They consist of a single RNA motif which catalyzes a reversible, site-specific cleavage of one of its own phosphodiester bonds . Truncation of this motif allowed a minimal HHRz to be constructed which was the very first ribozyme to be crystallized. HHRz minimal motifs are characterized by a core of eleven conserved nucleotides (bold font in Figure 20) from which three helices of variable length radiate. Selective mutation of any of these conserved residues results in a substantial loss of activity. In the absence of metal ions the structure is relaxed ( extended ), but upon addition of Mg +, hammerhead ribozymes spontaneously fold into a Y-shaped conformation (Figure 20 Color Plate 3). ... 

Z-form DNA is a more radical departure from the B structure the most obvious distinction is the left-handed helical rotation. There are 12 base pairs per helical turn, and the structure appears more slender and elongated. The DNA backbone takes on a zigzag appearance. Certain nucleotide sequences fold into left-handed Z helices much more readily than others. Prominent examples are sequences in which pyrimidines alternate with purines, especially alternating C and G or 5-methyl-C and G residues. To form the left-handed helix in Z-DNA, the purine residues flip to the syn conformation, alternating with pyrimidines in the anti conformation. The major groove is barely apparent in Z-DNA, and the minor groove is narrow and deep. 

---