TOPICS IN NUCLEIC ACID STRUCTURE

Increasing attention is being devoted to the three-dimensional conformation of molecules, with emphasis on macromolecules of biological interest such as proteins and nucleic acids and, especially, the interaction in three-dimensional space between enzymes and their substrates and inhibitors, between nucleic acids and selected drugs, etc. Such studies furnish not only fundamental biochemical information, but are currently profited from in attempts to design more effective drugs. The experimental methods of choice for delving into the spatial conformation of both small and large molecules are X-ray diffraction (of crystals and tibres) and nuclear magnetic resonance spectroscopy. The present small volume includes 9 contributions by various specialists, based on the use of these techniques. There is a useful (but all too short) digression in ch. 4, by Struthers Arnott, on the relative merits of other techniques, such as circular dichroism and infrared linear dichroism. One of the contributions, by D.M.J. Lilley, describes briefly the utility of neutron diffraction in studies on eukaryotic chromatin structure. The reader will find in this volume concise descriptions of the crystal and solution conformations of fragments of DNA and RNA and, in particular, of polynucleotides, both synthetic and natural. The final two chapters describe the use of Xray diffraction and NMR to elucidate the solid state and solution conformations of polynucleotide-drug complexes, an area of considerable interest in the field of drug development. The comparisons between results obtained by diffraction and NMR are perhaps not as extensive as might be desired, but this is due in part to the sparsity of data on NMR spectroscopy of oligonucleotides. Somewhat surprising is the absence of any reference to results on high resolution 3tP NMR of polynucleotide fibres, which can be directly compared with X-ray diffraction results on the same fibres. The emphasis throughout the volume is on the results obtained, and their interpretation, rather than on details of the experimental techniques involved. This undoubtedly renders the contents more accessible to the molecular biologist. Chapter 1, by Helen Burman, summarizes in readable form the basic nomenclature employed to describe the conformational parameters of oligoand polynucleotides; and the non-specialist will of necessity have to refer back to this chapter. . . one of the prices we must all pay for the accelerated rate of specialization that afflicts almost all fields now (but at least provides an occupation, usually not a simple one, for those interested in nomenclature). Most of the figures are very well done. Particularly interesting to this reviewer was tig.5.4 on p. 92, showing all the tertiary base pairs in the crystal structure of tRNAPhe, with base pairings different from the Watson-Crick type. One error was noted, viz. fig. 1.2 (a) on p. 3, showing Lribofuranose instead of D-ribofuranose, and obviously due to an oversight by the draughtsman. The Editor states in his preface that ‘It is inevitable that a book of this nature becomes dated all too quickly . . .’ actually a good deal of the material in this volume will not be rapidly outdated, but rather undergo further development, as is natural. For example, although published in 1981, it appears clear, from a perusal of the contents, that the manuscripts were actually submitted in 1979, so that two of the contributors had barely the opportunity to refer to the initial exciting events linked to the discovery of Z-DNA, first reported in the crystal form by van Boon, Rich and their collaborators in 1979, and for which there is now evidence of its existence in biological systems. Presumably subsequent projected volumes in this series will include accounts of these, and other, new advances.