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Acta Cryst. (1993). D49, 602-603

Macromolecular crystallography with synchrotron radiation

By J. R. Helliwell

Pp. xx + 595. Cambridge University Press, 1992
Price £95.00, US $165.00. ISBN 0-521-33467-5

The generation of a new scientific discipline, or advent of a new technique, is often marked by a progression from frontier scientific articles, to review articles and conference proceedings, to scholarly monographs and, finally, to graduate and undergraduate texts. John Helliwell made major contributions, through his scientific articles and conference presentations, to the birth of synchrotron-based macromolecular crystallography. This reviewer's copies of his review articles on this topic, written separately and with Trevor Greenhough, are dog-eared and battered - testimony that they are widely used and full of essential information. The present book is certain to suffer the same, surely desirable, fate! Aimed at researchers in a variety of disciplines spanning the biological and physical sciences, it reviews the theoretical and experimental foundations of conventional macromolecular crystallography before presenting a comprehensive description of the generation and nature of synchrotron radiation, of the instrumentation needed to harness the radiation and deliver it to the target crystal, and of the experimental techniques, both monochromatic and Laue, that exploit the radiation effectively and demonstrate its applicability to a wide range of problems in modern structural biology. For biochemists and biologists who conduct experiments at synchrotron sources, it answers the questions: `what's upstream from my experiment?' and `how do the X-rays get from the source to my crystal?' For the physicists and engineers who design the synchrotron sources or the beam lines, it answers different questions: `just what are the structural biologists and crystallographers up to? Why do they demand (for example) such a tightly focused, stable, rapidly tunable, monochromatic X-ray beam? Are experiments on virus crystals really brilliance-driven?' Given the diversity of interests and backgrounds of the intended readers, it is a particular strength of the author that he presents much complex material in a straightforward and generally comprehensible style. Although some topics, such as the fundamentals of crystallography, are dealt with only briefly, they are amply described in other texts, and the comprehensive reference list provides enough pointers to the research literature to satisfy the most enthusiastic reader. The numerous line drawings are of high quality, but the halftone prints seem to have suffered severely in the production process, and they are of more limited value.

Besides describing the present state of play, Helliwell offers many pointers to the next innings, so much so that a researcher looking for novel topics to pursue in the next grant application will find several here. As an example, a chapter is devoted to diffuse X-ray scattering from macromolecular crystals, where the high information content of the diffraction pattern is immediately apparent, but where the means of extracting that information in structural terms remain to be fully developed. Another chapter deals with ongoing developments in Laue diffraction, both static and time-resolved, and there are speculations on, inter alia, the use of ultra-short X-ray wavelengths, novel X-ray detectors, and the use of Bijvoet ratios rather than differences.

Today, conducting experiments at a synchrotron rather than in the home laboratory is always more complicated, subject to extreme time pressures and often more stressful. It is an enterprise to be undertaken only when the scientific benefits are marked. However, with the arrival of powerful and accurate multiple-wavelength anomalous dispersion (MAD) phasing techniques, where the experimental measurements are most readily made with synchrotron radiation, it seems likely that quite soon the majority of macromolecular crystallographers - not just those studying virus structure, or microcrystals, or exotic time-resolved problems - will choose to use synchrotron sources. This book will be their one essential reference.

Keith Moffat

Dept. of Biochemistry and Molecular Biology
The University of Chicago
920 East 58th Street
IL 60637

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