DNA principle

The first six chapters of this book deal with the basic principles of protein structure as we understand them today, and examples of the different major classes of protein structures are presented. Chapter 7 contains a brief discussion on DNA structures with emphasis on recognition by proteins of specific nucleotide sequences. The remaining chapters illustrate how during evolution different structural solutions have been selected to fulfill particular functions. 

Pabo, C.O., Sauer, R.T. Transcription factors structural families and principles for DNA recognition. 

The world of zinc-containing DNA-binding proteins is by no means exhausted by these three subfamilies. Several other subfamilies are already known with different three-dimensional structures and different sequence patterns of cysteine and histidine residues that form the zinc ligands. Further subfamilies may well be discovered as the genomes of different species are sequenced whether or not any fundamentally new principles for DNA-protein recognition will be discovered amongst these new subfamilies remains to be seen. 

The ability of the leucine zipper proteins to form heterodimers greatly expands the repertoire of DNA-binding specificities that these proteins can display. As illustrated in Figure 10.19, for example, three distinct DNA-binding specificities could, in principle, be generated from two types of monomer, while six could be created from three types of monomer and so on. This is an example of combinatorial control, in which combinations of proteins, rather than individual proteins, control a cellular process. It is one of the most important mechanisms used by eucaryotic cells to control gene expression. 

Biological fibers, such as can be formed by DNA and fibrous proteins, may contain crystallites of highly ordered molecules whose structure can in principle be solved to atomic resolution by x-ray crystallography. In practice, however, these crystallites are rarely as ordered as true crystals, and in order to locate individual atoms it is necessary to introduce stereochemical constraints in the x-ray analysis so that the structure can be refined by molecular modeling. 

DNA synthesizers operate on a principle similar to that of the Merrifield solid-phase peptide synthesizer (Section 26.8). In essence, a protected nucleotide is covalently bonded to a solid support, and one nucleotide at a time is added to the growing chain by the use of a coupling reagent. After the final nucleotide has been added, all the protecting groups are removed and the synthetic DNA is cleaved from the solid support. Five steps are needed ... 

Alec Jeffryes, an English geneticist, discovered in the 1980s how to apply this principle to forensics. To do this, it is necessary to locate that portion of the DNA molecule in which the base sequence differs significantly from one individual to another. That part of the molecule is cut out by a "restrictive enzyme" in much the same way that trypsin splits a protein molecule into fragments. The DNA sample obtained in this way from a suspect can be compared with that derived from blood, hair, semen, saliva, and so on, found at the scene of a violent crime. 

At least in principle, comparison of DNA fingerprints can determine the guilt or innocence of a suspect beyond a reasonable doubt. 

When induced in macrophages, iNOS produces large amounts of NO which represents a major cytotoxic principle of those cells. Due to its affinity to protein-bound iron, NO can inhibit a number of key enzymes that contain iron in their catalytic centers. These include ribonucleotide reductase (rate-limiting in DNA replication), iron-sulfur cluster-dependent enzymes (complex I and II) involved in mitochondrial electron transport and cis-aconitase in the citric acid cycle. In addition, higher concentrations of NO,... 

Terminase inhibition is an antiviral approach that may also be of consequence for other members of the herpesvirus group. In addition, since a similar DNA maturation process does not occur in higher cells, this principle offers the potential for high selectivity, in contrast to many of the viral DNA polymerase inhibitors, which also interact with cellular enzymes and hence can have severe side effects. 

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