Nucleotide Bases/base pairs

Owing to the central role of DNA in biochemistry and biophysics, the computation of the electronic structure of periodic polymers constructed from nucleotide bases, base pairs, and nucleotides by applying the ab initio Hartree-Fock crystal-orbital method has attracted much... 

Due to the central role of DNA and proteins in biochemistry and biophysics the computation of the electronic structure of periodic polymers built from nucleotide bases, base pairs, nucleotides and amino acids, respectively, had been of high interest since about twenty years. Early calculations of the band structure of DNA related periodic polymers have been performed with the crystal orbital (CO) method on the basis of different semiempirical levels (1). Recently the results of ab initio Hartree-Fock CO (2, 3) band structure calculations for the four nucleotide base stacks (4-6), the two Watson-Crick base pair stacks (6), the sugar-phosphate chain (4,5) and the three nucleotides cytidine (4,5), adenylic acid and th3nnidine (6) have been reported. These computations represent a significant progress but the following improvements are required for a more accurate description of the electronic structure of real DNA and its transport properties ... 

Structural Insights, Nucleic Acids offers a three-dimensional perspective on nucleotide structure, base pairing, and other aspects of DNA and RNA structure. 

Position of nucleotide or base pair Composition in Composition in ... 

The major catalytic step of DNA synthesis is shown below. Notice that DNA synthesis always occurs in a 5 to 3 direction and that the incoming nucleotide first base pairs with the template and is then linked to the nucleotide on the primer. (Fig 11.20)... 

The answer is e. (Murray, pp 452—467. Sciivei pp 3—45. Sack, pp 1—40. Wilson, pp 101-120.) For transfer RNAs, the 5 end is often guanosine and is always phosphorylated, while the 3 end is CCA. Although transfer (t) RNA molecules have many features in common, the primary feature that sets them apart is their specificity for different amino acids and the corresponding specific differences of their anticodons. Each tRNA is an L-shaped single chain composed of up to 93 ribonucleotides. Each contains up to 15 methylated bases, and about half of the nucleotides are base-paired into double helices. Activated amino acids attach to the terminal 3 -hydroxyl group of the adenosine. 

Water is an essential part in the biomacromolecular system, which is mainly responsible for the structure and functions of nucleic acids, proteins, and other constituents of cell [136-138]. Both proteins and DNA are generally hydrated. It is well known that the conformation of DNA is sensitive to hydration, and presence of salts and ligand molecules [112, 138]. The nucleic acids have three levels of water structure. About 12 water molecules per nucleotide are involved in the primary hydration shell [107, 112, 137, 138]. The water molecules present in the primary shell are impermeable to cations and do not form ice on freezing. The secondary level is permeable to cations and forms ice on freezing and third level is the completely disordered, so-called bulk water. Several theoretical studies have been carried out on the level of hydration on DNA bases, base pairs, base stacks, and double helical DNA [107, 121, 131, 139]. Both the experimental and molecular simulation studies have clearly brought out the importance of hydration in DNA and RNA structures [140-147]. 

The m-RNA strand is thus arranged in a series of units, each three bases long, each of which represents, or codes for, a particular amino acid. Corresponding to these three m-RNA bases are a complementary set of three bases on the arm of the t-RNA molecule directly opposite the arm which binds the amino acid, and these three nucleotides form base-pairs with the m-RNA triplet on the ribosome. Bach triplet of three bases along the m-RNA is termed a codon the complementary triplet on the t-RNA is called an anti-codon. 

Base analogues. Because their structures are similar to the normal nucleotide bases, base analogues can be inadvertently incorporated into DNA. For example, caffeine is a base analogue of thymine. Because it can base pair with guanine, caffeine incorporation can cause a transition mutation. 

Transcription, the synthesis of RNA from a DNA template, is carried out by RNA polymerases (Fig. 14.2). Like DNA polyma-ases, RNA polymerases catalyze the formation of ester bonds between nucleotides that base-pair with the complementary nucleotides on the DNA template. Unlike DNA polymerases, RNA polymerases can initiate the synthesis of new chains in the absence of primers. They also lack the 3 to 5 exonuclease activity found in DNA polymerases. A strand of DNA serves as the template for RNA synthesis and is copied in the 3 to 5 direction. Synthesis of the new RNA molecule occurs in the 5 to 3 direction. The ribonucleoside triphosphates ATP, GTP, CTP, and UTP serve as the precursors. Each nucleotide base sequentially pairs with the complementary deoxyribonucleotide base on the DNA template (A, G, C, and U pair with T, C, G and A, respectively). The polymerase forms an ester bond between the a-phos-phate on the ribose 5 -hydroxyl of the nucleotide precursor and the ribose 3 -hydroxyl at the end of the growing RNA chain. The cleavage of a high-energy phosphate bond in the nucleotide triphosphate and release of pyrophosphate (from the (3 and y phosphates) provides the energy for this polymerization reaction. Subsequent cleavage of the pyrophosphate by a pyrophosphatase also helps to drive the polymerization reaction forward by removing a product. 

The general t-RNA structure is characterised by four main arms and a minor extra arm which is of variable size (Figure 11.40). Some unusual bases are always present and about half the nucleotides are base-paired. In addition to the anticodon arm there is the DHU arm which contains up to three dihydrouridine residues, and the T j/C arm containing the T /C sequence of bases. The amino... 

Among the 76 nucleotides of tRNA are two sets of three that are especially important The first is a group of three bases called the anticodon, which is comple mentary to the mRNA codon for the ammo acid being transferred Table 28 3 lists two mRNA codons for phenylalanine UUU and UUC (reading m the 5 3 direction) Because base pairing requires the mRNA and tRNA to be antiparallel the two anticodons are read m the 3 5 direction as AAA and AAG... 

In the human cell there are 23 pairs of chromosomes containing approximately 3000 million base pairs of DNA. Short sequences of DNA, perhaps with as few as 20 nucleotide units and sometimes radiolabeled, can be obtained either by chemical synthesis (gene machine) or from cloning. These short sequences can be used to probe for a complementary sequence by looking for the position to which they bind to any DNA sample under investigation, from blood for example. Such probes can detect as little as 100 fg of DNA and are the basis of forensic genetic fingerprinting tests. 

DNA polymerase enzymes all synthesize DNA by adding deoxynucleotides to the free 3 -OH group of an RNA or DNA primer sequence. The identity of the inserted nucleotide is deterrnined by its abiHty to base-pair with the template nucleic acid. The dependence of synthesis on a primer oligonucleotide means that synthesis of DNA proceeds only in a 5%o V direction if only one primer is available, all newly synthesized DNA sequences begin at the same point. 

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 protein-DNA interactions have been analyzed in detail at high resolution in the complex between the 434 repressor fragment and the ORl containing 20mer DNA. A pseudo-twofold symmetry axis relates the halves of this complex. The symmetry is not exact since the nucleotide sequence of the DNA is slightly different in each half (see Table 8.2). However, the interactions between one protein subunit and one half of the DNA are very similar to those between the second subunit and the other half of the DNA since most of the bases that interact with the protein are identical in both halves. Details of the interaction are very similar to those in the complex with the palindromic synthetic 14mer of DNA shown in Figures 8.14 and 8.15. The base pairs at one end of the DNA, 1-14, 2-13, etc. are called base pairs 1, 2, etc. 

Figure 9.19 Nucleotide sequence of the 21-base pair DNA fragment cocrystalUzed with the DNA-binding domain of p53. The p53 binds in a sequence-specific manner to the shaded region.

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

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