|The IUCr is an International Scientific Union. Its objectives are to promote international cooperation in crystallography and to contribute to all aspects of crystallography, to promote international publication of crystallographic research, to facilitate standardization of methods, units, nomenclatures and symbols, and to form a focus for the relations of crystallography to other sciences.|
Fourier methods for the determination of crystal structures were first mentioned by W. L. Bragg in 1929, this technique was then used successfully by Beevers and Lipson for determining the structure of CuSO4.5H2O in 1934. Beevers and Lipson were trying to understand the structure of the triclinic crystal with two formula units in the unit cell when Beevers suggested using the Fourier method, which at the time was being suggested by Bragg for the determination of structures.
The problem of the technique came in the summation as there were 95 intensities and because of the resolution limitations it was decided five hundred points would have to be considered in the asymmetric unit.
Some trial and error ensued before in 1936 Lipson devised a method which saved a considerable amount of time and effort, and so the Fourier strips came to being. They were trialed to a wider audience with 70 sets being sold or given to laboratories in the first few years, Beevers continued to produce sets of the strips, until production declined as calculating machines and computers began to emerge.
A symposium at the University of Liverpool has been organized to celebrate the achievements of Lipson & Beevers in the presence of a number of family members of Henry Lipson.
The Barkla X-ray laboratory of Biophysics at the University of Liverpool was opened on July 21, 2011 by Sir Tom Blundell and the late Dame Louise Johnson. Charles Glover Barkla was a graduate and then lecturer at the University, as were both Arnold Beevers and Henry Lipson during their time. Barkla made a number of key contributions to the birth of X-ray physics and crystallography for which he received the Nobel Prize for Physics in 1917.
An X-ray exhibition will be opened at the end of the symposium celebrating the achievements of Sir Oliver Lodge (the first physics Professor of the University in 1881), Barkla, Beevers & Lipson.The event which will take place on July 17, 2015 is free to attend. To register for the event please complete this form.
Parasitic protozoa cause a range of diseases which threaten billions of human beings. They are responsible for tremendous mortality and morbidity in the least-developed areas of the world. In a special issue of Acta Crystallographica Section F: Structural Biology Communications dedicated to molecular parasitology Professor Wim G. J. Hol presents an overview of the evolution of structure-guided design of inhibitors, leads and drug candidates aiming at targets from parasitic protozoa [Hol, W. G. J. (2015). Acta Cryst. F71, 485-499; doi:10.1107/S2053230X15004987]. The article also contains a selection of examples where crystal structure determinations have assisted in the development of compounds which became promising drug candidates.
The impact of parasites on human life has been and still is profound. Diseases caused by these protozoa occur most frequently in tropical areas, most intensively and tragically in the poorest populations. Underlying causes include poor water sanitation, intensive contact with intermediate vectors, lack of public health infrastructure and other factors.
A major concern is that the number of well tolerated therapeutics is very limited, or even absent, for essentially all of these parasitic diseases. The only exception is malaria, where a number of therapies have had some success.
A pioneering international effort to combat tropical maladies, including protozoan diseases, has been the creation of the UNICEF/UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases, abbreviated as TDR. This programme celebrated 40 years of existence in 2014. TDR with limited resources successfully managed to make the world more aware than ever before of a whole set of largely unrecognised tropical diseases. TDR was also able to leverage additional funds to promote research in this field.
Protozoan parasites have developed sophisticated mechanisms to circumvent human defense systems, which make the development of effective and affordable vaccines for the parasitic protozoa an enormous challenge. Therefore therapeutic compounds and in particular combinations of compounds, are likely to remain a cornerstone of antiparasitic strategies for a long time.
Structural information on drug targets can contribute to many stages of the long road leading to such compounds. Hence, it is encouraging that the number of three-dimensional structures of proteins from human parasites is approaching 2000. The challenge is to increase this body of knowledge and also to convert this three-dimensional information into compounds which prevent the diseases caused by these organisms. Three-dimensional structures can not only guide the design of compounds with great potency, but can also be of assistance in lead-optimization stages of drug discovery, when the selectivity, bioavailability, pharmacodynamics, pharmacokinetic, safety, formulation and other properties of the compound have to be improved.
The future requires increasing scientific and financial contributions from governmental, non-profit and for-profit institutions. While there is reason for considerable optimism for success in the coming years, formidable obstacles remain to be overcome before we are anywhere near the situation that was once the case in the field of antibiotics, where a broad arsenal of drugs was available. Even that arsensal is now hardly sufficient any more. This is a major lesson and emphasizes the need for the design of multiple new therapeutics for patients infected by parasitic protozoa.
Turning one-dimensional diffraction from polycrystalline (powder) samples, particularly from multiphase samples, into three-dimensional single-crystal diffraction patterns has long been regarded as a difficult, if not impossible, task [Hao, Q. (2015). IUCrJ 2, 307-308; doi: 10.1107/S2052252515004017]. A group of scientists from China and the United States [Zhang et al. (2015). IUCrJ 2, 322-326; doi: 10.1107/S2052252515002146] have demonstrated that with the latest X-ray free-electron lasers (XFELs) and sample delivery technology, single-crystal diffraction patterns can be collected from multiphase polycrystalline samples and then the molecular structures can be solved ab initio.
The development of XFELs has opened up new opportunities for experiments that seem impossible now to become a reality in the near future. One of the new capabilities of XFELs is to collect single-crystal diffraction data from randomly oriented sub-micron-sized crystals using serial femtosecond crystallography (SFX).
Many materials with applications across many industries such as zeolites are polycrystalline (powders) and cannot be grown as single crystals. Furthermore, different types of samples (multiphase) may be mixed during production of a material; for example, zeolite NU-87 may occur as an impurity in zeolite TNU-9. X-ray diffraction from such samples will usually result in a one-dimensional powder pattern. Because of the relatively large molecular size, the powder diffraction pattern from a zeolite can be difficult to interpret. The powder diffraction pattern from a mixture of TNU-9 and NU-87 would be impossible to process.
Powder samples are essentially a mixture of sub-micron-sized single crystals. In this study Zhang et al. have proposed the use of serial crystallography to turn powder diffraction into single-crystal diffraction. A test has been performed on a mixture of zeolite using simulated diffraction patterns. X-ray diffraction snapshots by SFX were simulated and processed; identification according to the primitive unit-cell volume determined from individual snapshots was able to separate the whole set of snapshots in to two subsets, which matched the two zeolites in the sample. Monte Carlo integration was then applied to them separately. Two sets of three-dimensional single-crystal diffraction intensities could then be derived. The crystal structures of the two zeolites were solved using the direct methods program SHELXD with default parameters.
This technique promises to open up new avenues for the study of many important polycrystalline materials that cannot be analysed by conventional X-ray powder diffraction methods.
The proteins expressed by plants under stressful conditions (such as drought, salinity or pathogen invasion), known as pathogenesis-related (PR) proteins, have been divided into 17 classes. The members of most of these classes have well known biological activity. PR proteins of class 10 (PR-10) are very unusual, because no unique function can be assigned to them despite their abundance, their co-existence as many isoforms in one plant, and many years of study.
Hyp-1 is a PR-10 protein from St John’s wort (the medicinal herb Hypericum perforatum). To shed more light on Hyp-1 and on PR-10 proteins in general, Hyp-1 was crystallized in complex with the fluorescent probe 8-anilino-1-naphthalene sulfonate (ANS), and the crystal structure was solved by molecular replacement using Phaser, despite tetartohedral twinning and a huge unit cell with severe pseudosymmetry, including sevenfold translational non-crystallographic symmetry (tNCS) along c. tNCS was handled in Phaser using new maximum-likelihood algorithms, but the space group ambiguity introduced by the twinning had to be overcome by searching for 56 protein molecules in P1 symmetry [Sliwiak, J. et al. (2014). Acta Cryst. D70, 471-480; doi: 10.1107/S1399004713030319]. Ultimately, the crystal structure of the Hyp-1/ANS complex could be described at 2.4 Å in the C2 space group, with 28 well ordered protein molecules and 89 ANS ligands, 60 of which populate three novel binding sites of this PR-10 molecule. In its description presented in detail by Sliwiak, J. et al. [(2015). Acta Cryst. D71, 829-843; doi: 10.1107/S1399004715001388], this superstructure can be considered as commensurately modulated within a supercell sevenfold extended in the c direction, consistent with a peculiar modulation in the diffraction pattern, showing intensity crests at l = 7n ± (0,3). The paper also discusses the possible pitfalls of twinning detection in cases of severe pseudosymmetry.
In a recent interview Professor Mariusz Jaskólski explains why he feels that crystallography in Poland is so strong, firstly because of the long standing school of crystallography based there and secondly how crystallography plays on a range of sciences which Poland already excels in, such as physics, biology, medicine and mathematics.
Jaskólski’s work with co-workers based in Poland, United Kingdom and the United States [Sliwiak, J. et al. (2015). Acta Cryst. D71, 829-843; doi: 10.1107/S1399004715001388] is an excellent example of the collaborative efforts, so frequent in our discipline.
John Spence main editor of IUCrJ is one of the latest Foreign Members of the Royal Society announced 1 May 2015. Professor John Spence is distinguished for his innovative world-leading contributions to both biology and materials science. He led the team which conceived the first application of X-ray free-electron lasers (XFELs) to structural biology using protein nanocrystals and he pioneered femtosecond serial crystallography. He is also a world leader in the development and application of atomic-resolution electron microscopy, he co-invented a widely used technique for locating impurity atoms in nanocrystals and published the first observation of dislocation kinks, at atomic resolution. He has developed new microscopies and spectroscopies which have given scientists new eyes to understand atomic processes in solids.
You can see a full list of John’s papers published in IUCr journals here.
This article is reprinted from material taken from The Royal Society, with editorial changes made by IUCr.
The May issue of Acta Crystallographica Section F Structural Biology Communications (http://journals.iucr.org/f) is a dedicated special issue on the structural investigation of proteins associated with molecular parasitology, specifically research linked to protozoan pathogens. Parasitic protozoa threaten the lives of millions of human beings by causing a range of diseases including malaria, leishmaniasis, Chagas disease, toxoplasmosis and African sleeping sickness.
Researchers have sought to understand the processes that allow pathogens to exist, to invade a host, to evade the immune response and to cause these debilitating and often fatal diseases. Structural biology, and in particular crystallography, complements such investigations. It can play a key role in drug discovery by providing accurate chemical information to guide the assessment of drug targets and computational design projects, in the search for pharmaceutical compounds.
The publication of this special issue represents an exciting new departure for Acta Crystallographica Section F. The journal hopes to provide a natural home for new research in molecular parasitology, as well as welcoming contributions from the structural biology community as a whole.This special issue includes fundamental studies in molecular parasitology and also research directed toward protozoan drug target characterization, including both NMR and crystal structures. The articles include an overview and perspective from Professor Wim Hol, an inspirational champion for the role of crystallography in drug discovery. There is also a short review from Professor Inari Kursula on cytoskeletal proteins related to the infection process, a topic that may provide opportunities in future drug discovery work.