2004 was a very busy year at the Macromolecular Crystallography (MX) beamlines of the ESRF (ID14 A&B, ID29, ID23-1). Nearly 600 separate experimental sessions were used and more than 2000 visiting scientists performed experiments at the MX beamlines. About 20% of the experimental sessions involved industrially-related activities, in particular the MXpress service, which continues to go from strength to strength. As in previous years this high throughput of visits and experimental sessions could not be sustained without the excellent support provided by the User and Travel offices, Experiments Division secretarial support and the ESRF Support Groups and Services. Routine operation of the ID23-1 end-station began, as planned, in April 2004 and both provided a valuable new addition to the facilities in the MX beamline portfolio and allowed the number of shifts provided to the User Community to increase slightly at a time when several of our more well-established end-stations were briefly closed to allow the installation and commissioning of new equipment and software designed to further improve their user-friendliness and automation. Almost all the end-stations are now equipped with micro- or mini- diffractometers and, in our now annual review of progress towards full beamline automation, J. McCarthy summarises developments in this area (Beamline Automation).

The MX External Scientific Programme continues to provide research highlights resulting in publications in Journals of the highest quality and impact. The article by Sørensen et al., Loading the Calcium Pump, summarises investigations of conformational changes in the structures of transmembrane cation pumps the results of which originally appeared in Science magazine as did the results of studies on bacterial nitric oxide (NO) signalling by Nioche et al., Crystal Structure of a Bacterial Sensor: Nitric Oxide Signalling Unveiled. As NO signalling is vital to the efficient functioning of drugs such as Viagra®, the interest in this latter work is perhaps understandable!

Also presented here are other examples of Structural Biology research, of interest to both the scientific community and the general public alike, such as the crystal structures of a human rhinovirus (the cause of the common cold) bound to a fragment of its cellular receptor (Verdaguer et al., X-ray Structure of a Minor Group Human Rhinovirus Bound to a Fragment of its Cellular Receptor Protein) and those that allowed the elucidation of the structure of heamagglutinin of the 1918 Influenza virus (Gamblin et al., The Structure and Receptor Binding Properties of the 1918 Influenza Haemagglutinin). The results of this latter work were extensively reported in the news media as they provided an explanation of the virulence of the 1918 'flu pandemic that caused the death of an estimated 20 million people. Also of general public interest was a report by the Cancer Genome Project (Wan et al., Investigating the Molecular Mechanism of Oncogenic Mutations of B-RAF) describing investigations into the effects of point mutations on the activity of the product of the B-RAF gene. Several such mutations convert B-RAF into an oncogene and the results of this work provided structural reasons for this. This latter work was carried out on ID13 and illustrates how some ESRF beamlines that are not dedicated full-time to MX can also provide significant contributions to the field. The CRG beamlines BM14, BM16 and BM30A, also provided significant amounts of beamtime for use in the External Scientific Programme of the ESRF. An excellent example of the science performed on the these beamlines is the report by Stuart et al. (The Structure of Bacteriophage f12 Packaging ATPase: An RNA Packaging Motor Caught in Action), describing the analysis of the structures, in different catalytic states, of the virus motor protein P4 which packages RNA in bacteriophage 12. These studies provide the first insights into the mechanism of the active packaging of RNA in viral capsids.

The In-House research carried out by the scientists, post-doctoral researchers and Ph.D. students associated with the MX beamlines also continues to develop apace. As ever this is based upon three building blocks: methods development; collaboration with external groups and the ESRF MX Group's own projects centring on the structural genomics of the radiation-resistant bacterium Deinococcus radiodurans. Three reports included here illustrate the two former aspects: The report by Ravelli et al. (A Structural Journey into Tubulin Regulation) shows how methodological developments ­ particularly those exploiting radiation damage ­ can help tip the balance between success and failure for difficult, but biologically-interesting projects. That by Brzezinski et al. (Development of a Bacterial Biosensor for Nitrotoluenes: the Crystal Structure of the Transcriptional Regulator DntR) is the first fruit of a collaboration between ESRF scientists and those at the University of Stockholm, the aim of which is the development of a bacterial biosensor that will allow the detection of carcinogenic nitroaromatic compounds. Finally, the article by Alzari et al. (The Crystal Structure of Glycogen Synthase) sheds light on the structure and mechanism of Glycogen Synthase, an important enzyme involved in one of the metabolic pathways used for the catalytic conversion of glycogen which is the major source of energy in most living organisms.

What does 2005 hold in store for MX activities at the ESRF? The construction and commissioning of ID23-2 will be completed during the second half of the year. This microfocus beamline will provide a welcome and significant addition the facilities available at the ESRF. Additionally, the new laboratory building for the Partnership for Structural Biology (PSB) will be completed, providing a new focus for Structural Biology both for the ESRF in particular and the Grenoble campus in general. Finally, efforts in beamline automation will continue: During 2005 all the MX beamlines (including the new ID23-2 end-station) will be equipped with ESRF/EMBL sample changers. This represents another significant step to the full automation of the MX beamlines so eagerly awaited by both ESRF scientists and external users alike.

G. Leonard and S. McSweeney