Editorial

At a session on the future of crystallography at the 1997 ACA Meeting in St. Louis, a group of prominent protein crystallographers (Wim Hol, Janet Smith, Judith Flippen-Anderson, Richard Harlow and Celerino Abad-Zapatero) led a discussion on the future of macromolecular crystallography. A major focus of the session was the rapidly expanding need for more access to synchrotron radiation facilities for macromolecular  crystallography. It was noted that the logical extension of the Genome Project will be an exponential growth in the need and demand for X-ray structure determination of new proteins and new members of protein families for which previous structures exist. This topic was also eloquently addressed at the 17th European Crystallographic Meeting in Lisbon in a plenary lecture presented by Tom Blundell. The elucidation of the gene or genes responsible for disease may do little to reveal the molecular details of the disease mechanism or the means of developing new therapies. That may require knowledge of the three-dimensional structure of the gene products, the nature of the active sites in those proteins, the sites of lethal mutation in those proteins, and the precise relationship of mutations to malfunction. Only X-ray crystallography can be relied upon to provide reliable and unambiguous information on these matters. X-ray crystallography will not be limited by the size of the macromolecule or macromolecular assembly. The only possible impediments will be availability of crystals, resources to collect data on those crystals, and computing facilities to refine and analyze the structures. The current demand for access to synchrotron facilities for macromolecular crystallographers causes at least a six month delay. The support of the development of resources to guarantee greater access to synchrotron facilities for crystallographers will become a growing need throughout the world.

This issue of the IUCr Newsletter contains the first of what we hope will be a series of terse summaries of {he state of the art of various aspects of the theory and application of crystallography and a forecast of the future. In an invited article, John Helliwell addresses the role of synchrotron radiation in the future of macromolecular crystallography on page 7.

Nobel Notes

Unless you have been hiding under a rock you know that the 1997 Nobel Prize in Chemistry was for studies elucidating the structure and function of adenosine triphosphate. The London Times on Oct. 16, 1997 reported that John Walker of the Medical Research Council's Molecular Biology Lab "spent 15 years studying this transmembrane pump using X-ray crystallography". Apparently the publication in Nature of the structure of mitochondrial FI-ATPase at 2.8Å resolution played a significant role in bringing 40 years of study by Paul Boyer to fruition. Coauthors with Walker of the 1994 Nature paper were J. P. Abrahams, A. G. Leslie, and R. Lutter from the Medical Research Council Lab of Molecular Biology, Cambridge, UK.

In the Newsletter of the Soc. of Crystallography in Australia, M. Guss notes that while crystallography may have made a critical contribution to the 1997 Nobel Prize in Chemistry, crystallography was not honored per se. The award illustrates that protein crystallography is now "a servant of biology and not an end in itself". In the early 1970's every new protein structure was a significant event as was each small molecule structure in the 1950's. These days hundreds of structures are solved each year and it is the significance of the chemistry, physics or biology that really matters.

The award of the Nobel Prize in Physiology and Medicine to Stanley Prusiner will only intensify a search for unequivocal demonstration of the structural basis for prion infection. Prusiner coined the term "prion" in 1982 to describe the "proteinaceous infectious particles" he believed caused scrapie in sheep and hamsters. He suggested that scrapie and a collection of other wasting brain diseases were due to a misfolded protein that propagates and kills brain cells. Numerous crystallographic groups around the world are attempting to determine the precise nature of the difference in conformation between prion molecules in the normal and disease states.