Phosphodiester conformations

The other important feature of the primary stmcture of RNA is the presence of the 2 -hydroxyl group in ribose. Although this hydroxyl group is never involved in phosphodiester linkages, it does impose restrictions on the heHcal conformations accessible to double-stranded RNA. 

The process of RNA synthesis in bacteria—depicted in Figure 37-3—involves first the binding of the RNA holopolymerase molecule to the template at the promoter site to form a PIC. Binding is followed by a conformational change of the RNAP, and the first nucleotide (almost always a purine) then associates with the initiation site on the 3 subunit of the enzyme. In the presence of the appropriate nucleotide, the RNAP catalyzes the formation of a phosphodiester bond, and the nascent chain is now attached to the polymerization site on the P subunit of RNAP. (The analogy to the A and P sites on the ribosome should be noted see Figure... 

Unlike other enzymes that we have discussed, the completion of a catalytic cycle of primer extension does not result in release of the product (TP(n+1)) and recovery of the free enzyme. Instead, the product remains bound to the enzyme, in the form of a new template-primer complex, and this acts as a new substrate for continued primer extension. Catalysis continues in this way until the entire template sequence has been complemented. The overall rate of reaction is limited by the chemical steps composing cat these include the chemical step of phosphodiester bond formation and requisite conformational changes in the enzyme structure. Hence there are several potential mechanisms for inhibiting the reaction of HIV RT. Competitive inhibitors could be prepared that would block binding of either the dNTPs or the TP. Alternatively, noncompetitive compounds could be prepared that function to block the chemistry of bond formation, that block the required enzyme conformational transition(s) of turnover, or that alter the reaction pathway in a manner that alters the rate-limiting step of turnover. 

In nucleic acids, the cross-correlation studies were applied to investigation of the sugar conformation [101-103] of the phosphodiester backbone [65] as well as to some more spe-... 

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... 

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). ... 

N 112 "Backbone Conformations in Secondary and Tertiary Structural Units of Nucteic Acids. Constraint in the Phosphodiester Conformation ... 

The possible backbone phosphodiester conformations in a dinucleotide monophosphate and a dinucleotide triphosphate are investigated by semiempirical energy calculations. Conformational energies are computed as a function of the rotations o and <0 about the internucleotide P-0(3 ) and P-015 1 linkages, with the nucleotide residues themselves assumed to be in one of the preferred [C(3 )-e/K/o) conformations. 

Figure 3. Contour diagram of the base stacking potential energy Kg of sequential adenine bases and the hydrogen bonding potential energy VHB of the complementary A T base pairs as a function of the phosphodiester rotation angles

Figure 6. Contour diagram of the distances d and d between successive Cl atoms in a DNA duplex as a function of the phosphodiester angles. The (X) denotes the conformation of the ideal theoretical helix of Figure 3 with d = d = 4.8 A. The shaded area on the diagram describes the local motions that preserve base stacking in a flexible duplex. See text for further explanation.

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