Open-access transformative agreements: is your institution included?

Volume 28, Number 1, 2020

ISSN 1067-0696

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Editorial

06 Apr 2020
Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19
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Visualizing an unseen enemy; mobilizing structural biology to counter COVID-19

Edward N. Baker

The COVID-19 pandemic currently sweeping round the world reminds us all of our vulnerability to ‘enemies’ we cannot see. In New Zealand we are all in lockdown for the next month, as are many populations, and none of us can see how long this will have to continue. Science of course holds the key to countering the pandemic, but our inability to ‘see’ the agent responsible generates fear, and, in some individuals, disbelief, while it also limits the strategies that can be applied.

Crystallography has a special role to play in this crisis. In its broadest sense, the term crystallography has come to embrace a range of approaches, from traditional single-crystal X-ray analysis through electron and neutron diffraction to cryo-electron microscopy (cryo-EM) and a variety of scattering technologies. Some are relatively mature, while others such as cryo-EM are undergoing revolutionary change. Collectively, they provide a uniquely powerful atomic scale view into the natural world, and when used judiciously, often in combination, can enable the three-dimensional structures of extremely complex molecules and molecular assemblies to be determined with sometimes breathtaking speed.

In many ways the current situation parallels that at the onset of the HIV-AIDS epidemic in the 1980s. In the absence of a straightforward route to a vaccine, crystal structures of key viral proteins, the HIV protease and reverse transcriptase, provided the crucial templates for structure-based drug design, and in a remarkably short space of time effective drugs became available for clinical use. This was arguably the ﬁrst great triumph for the use of crystallography in drug development. The virus responsible for the present COVID-19 pandemic, known as SARS-CoV-2, is very different from HIV. It belongs to the wider family of coronaviruses that includes those responsible for the SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome) outbreaks of 2003 and 2012, respectively. These viruses have trimeric protein ‘spikes’ on their surface that have attained an ability to attach to a receptor protein that is widely prevalent on cells of the human respiratory system: the ACE2 receptor. The virus also encodes two long overlapping polyproteins that are processed into smaller, functional, polypeptides that are essential for viral replication. The processing is carried out by two viral proteases, which are now of enormous interest as potential drug design candidates (as was the case for the HIV protease).

What is truly exciting, considering that at time of writing only three months have passed since COVID-19 was ﬁrst identiﬁed, is the speed with which some of these key structures have been determined. Already we have three-dimensional structures for three of them; the Main protease, M^pro, resolved by crystallography at 2.1 Å resolution by a Chinese group (Jin et al., 2020); the Spike protein, characterized by cryo-EM by two groups in the USA (Walls et al., 2020; Wrapp et al., 2020); and the viral RNA polymerase, characterized by cryo-EM in China (Gao et al., 2020). The structure of the human ACE2 receptor has also been solved by cryo-EM in China, in complex with the receptor-binding domain of the viral Spike protein (Yan et al., 2020). There is undoubtedly much more to come as researchers analyse the conformational changes that occur as receptor binding is followed by entry into cells, and target other key viral proteins.

Since its earliest days in the mid-1900s structural biology has been notable for a high degree of collegiality and willingness to share resources, methods and results. This, too, deserves to be celebrated as it is crucial that as many researchers as possible should bring their skills together at a time like this. One manifestation of this collegiality is the role of the worldwide Protein Data Bank (wwPDB), which makes the three-dimensional structural information for macromolecular structures freely available throughout the world. All of the SARS-CoV-2 structures so far determined have been deposited in the wwPDB, checked, annotated and released, most of them in advance of formal publication. This gives researchers anywhere the opportunity to participate in the search for therapies. Already, the M^pro structure has been the target of extensive screening in the search for potential drug leads, both by the Chinese researchers themselves and in the United Kingdom at the Diamond synchrotron facility. At the latter site a massive fragment screening exercise is in progress and a web-based call has been made for chemists, drug designers and others to contribute to the initiative.

At this point, research is accelerating and by the time this editorial is published and read, many more advances will have been made. One cannot know what the outcomes of these efforts will be, when a vaccine might become available or whether structure-based drug design will indeed produce effective drugs. My purpose in writing this editorial, however, is to applaud the energy and skill of the researchers, and their public spirit in sharing their results. And I take a vicarious pride in the fact that the discipline to which I have given my professional life – crystallography – has such an important role at a time of international crisis.

References

Gao, Y., Yan, L., Huang, Y., Liu, F., Zhao, Y., Cao, L., Wang, T., Sun, Q., Ming, Z., Zhang, L., Ge, J., Zheng, L., Zhang, Y., Wang, H., Zhu, Y., Zhu, C., Hu, T., Hua, T., Zhang, B., Yang, X., Li, J., Yang, H., Liu, Z., Xu, W., Guddat, L. W., Wang, Q., Lou, Z. & Rao, Z. (2020). bioRxiv, https://doi.org/10.1101/2020.03.16.993386.

Jin, Z., Du, X., Xu, Y., Deng, Y., Liu, M., Zhao, Y., Zhang, B., Li, X., Zhang, L., Peng, C., Duan, Y., Yu, J., Wang, L., Yang, K., Liu, F., Jiang, R., Yang, X., You, T., Liu, X., Yang, X., Bai, F., Liu, H., Liu, X., Guddat, L. W., Xu, W., Xiao, G., Qin, C., Shi, Z., Jiang, H., Rao, Z. & Yang, H. (2020). bioRxiv, https://doi.org/10.1101/ 2020.02.26.964882.

Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T. & Veesler, D. (2020). Cell, 180, 1–12.

Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S. & McLellan, J. S. (2020). Science, 367, 1260–1263.

Yan, R., Zhang, Y., Li, Y., Xia, L., Guo, Y. & Zhou, Q. (2020). Science, 367, 1444–1448.

This article was originally published in IUCrJ (2020). 7, 366–367; Acta Cryst. (2020). D76, 311–312 and Acta Cryst. (2020). F76, 158–159. It has also been included in a special virtual issue presenting articles and abstracts on coronaviruses that have been published in IUCr journals.

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IUCr journals news

02 Apr 2020
Open-access transformative agreements: is your institution included?
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Commentary

24 Mar 2020
There's many a good tune played on an old fiddle – a new colour for Alfred Werner's isomer counting
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There's many a good tune played on an old fiddle – a new colour for Alfred Werner's isomer counting

Edwin C. Constable

Chemical history often teaches that Alfred Werner (1866–1919) was the 'Founder of Coordination Chemistry' (Kauffman, 1966). In the sense that he was responsible for the modern vision of coordination chemistry and the clear distinction between oxidation number, Hauptvalenz, and coordination number, Nebenvalenz (Constable & Housecroft, 2013; Werner, 1893, 1911, 1920), this accolade is justified. However, as Bernal & Lalancette (2020) state in their publication in Acta Crystallographica Section C: Structural Chemistry, the reality is a little more complex.

Although Werner and his co-workers in Zürich were prolific experimentalists, most of these studies were performed after the publication of his seminal work of 1893 (Werner, 1893). In writing his Beitrag zur Konstitution anorganischer Verbindungen, Werner drew extensively on the large body of experimental work published by other chemists. Bernal & Lalancette (2020) particularly identify the compounds prepared by Sophus Mads Jørgensen (Kauffman, 1959) and Otto Linné Erdmann as being key elements in the development of his coordination model. This is not the place to revamp the controversy between Werner and Jørgensen, which is adequately documented elsewhere (Kauffman, 1960; Constable, 2019), although the interpretation is currently subject to some degree of revisionism (Kragh, 1997). It is certainly true that a vast number of the compounds used by Werner in developing his model were first prepared or characterized by Jørgensen or Erdmann, but this is also not the entire story.

The coordination chemistry of cobalt started at the end of the 18th Century CE with the description of what subsequently proved to be [Co(NH₃)₆]³⁺ by Tassaert (1798). This led to an exponential expansion of interest in cobalt chemistry in the following half century or so. Although the contributions of Jørgensen or Erdmann are exceptional, the contributions of Leoppold Gmelin, Emil Dingler, Karl Georg Winkelblech (Karl Marlo), Wilhelm von Beetz, Georg Vortmann, Frederic Just Claudet, Edmond Fremy and Karl Friedrich August Rammelsberg and many others are of equal importance (Constable, 2019). Among the unsung heroes of 19th Century coordination chemistry are Friedrich August Ludwig Karl Wilhelm Genth and Oliver Wolcott Gibbs who described a vast number of cobalt compounds in a series of publications in the 1850s and 1870s (Kauffman, 1977; Genth, 1851; Gibbs, 1873, 1875a,b; Gibbs & Genth, 1857a,b,c). They were also responsible for the popularization of the names for coordination compounds based on prefixes such as luteo-, croceo- and purpureo-, based on the colour of the prototype cobalt(III) complexes.

One of Werner's arguments for the octahedral coordination of complexes such as those of cobalt(III) relied on the number of isomers that could be isolated. Compounds of the type [CoA₄X₂]⁺ (A₄ = four amine N-atom donors and X = halido ligand) were a critical part of the establishment of the octahedral coordination geometry as opposed to a hexagonal planar one. Only two isomers, cis-[CoA₄X₂]⁺ and trans-[CoA₄X₂]⁺, were to be expected for octahedral complexes, whereas three would be found for a hexagonal planar one (Fig. 1). First described by Jörgensen (1889), the isolation of only two forms of [CoCl₂(en)₂]Cl, viz. violet cis-[CoCl₂(en)₂]Cl and green trans-[CoCl₂(en)₂]Cl, was one of the observations used to support the proposed octahedral geometry. The argument was that in no case had more than two isomers been found for [CoA₄X₂]⁺ complexes, although this is not an unambiguous establishment of the geometry, in particular because it relied on the non-observation of a third isomer.

Figure 1. The number of isomers expected for octahedral and hexagonal planar six-coordinate complexes.

Now, 131 years after the original publication by Jörgensen, the crystal structure of a new form of [CoCl₂(en)₂]Cl is reported by Bernal & Lalancette (2020). This compound is a purple form that contains equal amounts of the cis-[CoCl₂(en)₂]Cl and trans-[CoCl₂(en)₂]Cl isomers. It is really quite remarkable that this purple form has not been noted before, considering that the preparation of the cis-[CoCl₂(en)₂]Cl and trans-[CoCl₂(en)₂]Cl isomers is incorporated in so many undergraduate practical courses at universities around the world. The authors speculate what might have happened if Werner had been aware of, or if his co-workers had isolated, this form. It would probably not have demolished the case for the octahedral geometry, as this was built on evidence from more compounds than [CoCl₂(en)₂]Cl alone. Nevertheless, it would likely have caused him some sleepless nights!

This report is both interesting and important as it allows us to reassess the early work of Werner and brings an emphasis to the occurrence of cocrystals of complexes. Although the phenomenon of cocrystallization is well-established and investigated for organic compounds and pharmaceuticals, it is less well-documented or recognized in coordination chemistry. A search in Scifinder (https://www.cas.org/products/scifinder) for the terms ‘cocrystal’ and ‘cobalt’ combined yielded 234 hits, suggesting that there is a rich area for data-mining here.

References

Bernal, I. & Lalancette, R. A. (2020). Acta Cryst. C76, 298–301.

Constable, E. C. (2019). Chemistry, 1, 126–163.

Constable, E. C. & Housecroft, C. E. (2013). Chem. Soc. Rev. 42, 1429–1439.

Genth, F. A. (1851). Keller-Tiedem’s Nordamerikanischer Monatsbericht für Natur- und Heilkunde, 2, 8–12.

Gibbs, W. (1873). Am. J. Sci., Ser. 3, Vol. 6, pp. 116–125.

Gibbs, W. (1875a). Proc. Am. Acad. Arts Sci. 10, 1–38.

Gibbs, W. (1875b). Proc. Am. Acad. Arts Sci. 11, 1–51.

Gibbs, W. & Genth, F. A. (1857a). Am. J. Sci. 23, 234–265.

Gibbs, W. & Genth, F. A. (1857b). Am. J. Sci. 23, 319–341.

Gibbs, W. & Genth, F. A. (1857c). Am. J. Sci. 24, 86–107.

Jörgensen, S. M. (1889). J. Prakt. Chem. 39, 1–26.

Kauffman, G. B. (1959). J. Chem. Educ. 36, 521–527.

Kauffman, G. B. (1960). Chymia, 6, 180–204.

Kauffman, G. B. (1966). In Father of Coordination Chemistry. Berlin, Heidelberg: Springer-Verlag.

Kauffman, G. B. (1977). Isis, 68, 392–403.

Kragh, H. (1997). Br. J. Hist. Sci. 30, 203–219.

Tassaert, B. M. (1798). Ann. Chim. Phys. 28, 92–107.

Werner, A. (1893). Z. Anorg. Chem. 3, 267–330.

Werner, A. (1911). In New Ideas on Inorganic Chemistry. Translated, with the author’s sanction, from the second German edition. New York, Bombay, Calcutta: Longmans, Green and Co.

Werner, A. (1920). In Neuere Anschauungen auf dem Gebiete der anorganischen Chemie, 4th ed. Braunschweig: Friedrich Vieweg & Sohn.

This article was originally published in Acta Cryst. (2020). C76, 312–313.

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IUCr journals news

18 Mar 2020
IUCr Journals introduces its three Commissioning Editors
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IUCr Journals introduces its three Commissioning Editors

The IUCr is pleased to announce the appointment of three Commissioning Editors for IUCr journals. "The appointment of Commissioning Editors – to work across all relevant IUCr journals in commissioning high-quality individual papers and special issues, and hopefully attract authors, reviewers and editors who have not worked with IUCr journals previously – is new to IUCr journals," said Editor-in-Chief, Andrew Allen. "The Commissioning Editor role is envisaged to be comparable to that of a Section Editor and will involve extensive interaction with the journal Section Editors and Co-editors."

The three Commissioning Editors and their subject areas are as follows:

Biology: Roberto Steiner

Professor Steiner (Randall Centre for Cell and Molecular Biophysics, King’s College London, UK; roberto.steiner@kcl.ac.uk) has over 20 years of experience in the use of X-ray crystallography applied to understanding biological macromolecules and their mechanisms of action. He also has a strong passion for disseminating best practices in the field having been a tutor and contributor at many international schools and workshops. Roberto has published in a number of IUCr Journals and has served as a Guest Editor for a CCP4 issue of Acta Cryst. D. He is in the process of commissioning a special issue on serial crystallography and has selected a number of top articles that appear in a virtual special issue. While initially focusing on IUCrJ, Acta Cryst. D and Acta Cryst. F, Roberto intends to expand his work to the other journals with remits relevant to structural biology – especially Acta Cryst. A, J. Appl. Cryst. and J. Synchrotron Rad.

Chemical sciences (chemistry and chemical crystallography): Elena Boldyreva

Professor Boldyreva (Boreskov Institute of Catalysis, Russian Academy of Sciences and Novosibirsk State University, Novosibirsk, Russia; eboldyreva@catalysis.ru) was already well known to IUCr journals having served as a Co-editor for Acta Cryst. B for nine years, and more recently as a Main Editor of Acta Cryst. E. She has published in IUCrJ, Acta Cryst. A, Acta Cryst. B, Acta Cryst. C, Acta Cryst. E and J. Appl. Cryst.; however, her publications mainly focus on chemistry and chemical crystallography. Elena is using her extensive experience in dealing with the chemical crystallography community at the international level to forge a stronger interaction between this community and IUCr journals, and has a number of ideas for special issues, including Chemical crystallography and new materials, Chemical crystallography and drug research, Chemical crystallography and solid-state transformations, and virtual Editors' selection issues.

Materials, methods and instrumentation: Thomas Proffen

Dr Proffen (Neutron Sciences Directorate, Oak Ridge National Laboratory, Oak Ridge, TN, USA; tproffen@ornl.gov) has served as an active Co-editor of J. Appl. Cryst. since 2014. He has a distinguished publication record with many citations across much of the applied crystallography field, and has published in Acta Cryst. A, Acta Cryst. B, J. Appl. Cryst. and J. Synchrotron Rad. His main emphasis in publications is centred on materials, neutron scattering and applied crystallography, including advanced methods, software and instrumentation development. Thomas is conversant with the user communities of large-scale national and international facilities, and conducts various mentoring and outreach activities in support of young researchers, together with gender and ethnic diversity. He is developing plans for a special issue on machine learning in crystallography.

This inaugural team spans a subject, geographical and gender distribution that should serve well in developing the Commissioning Editor role for the IUCr journals. Once a successful operation is established, the appointment of a further Commissioning Editor from the developing world will be considered.

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IUCr journals news

18 Mar 2020
Acta Cryst. E welcomes Section Editors Sean Parkin and Graciela Díaz de Delgado
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Acta Cryst. E welcomes Section Editors Sean Parkin and Graciela Díaz de Delgado

Sean Parkin (left) and Graciela Díaz de Delgado, Acta Cryst E.'s new Section Editors.

Acta Crystallographica E: Crystallographic Communications has recently welcomed two new Section Editors: Sean Parkin (University of Kentucky, Lexington, KY, USA; s.parkin@uky.edu) and Graciela Díaz de Delgado (Universidad de Los Andes, Mérida, Venezuela; gdiazdedelgado@gmail.com). They have joined existing Section Editors Chiara Massera and Luc Van Meervelt in further developing Acta Cryst. E in its transformation to the IUCr's open-access structural communications journal for the rapid high-quality publication of fully validated structures.

Professor Parkin, already an experienced Co-editor of both Acta Cryst. E and IUCrData, was appointed in summer 2019 to succeed former Section Editor Elena Boldyreva, who had been selected as the IUCr Journals Commissioning Editor for Chemical sciences. Sean has published widely in the chemical and crystallographic literature, including nearly 150 papers in IUCr journals (Acta Cryst. A, Acta Cryst. B, Acta Cryst. C, Acta Cryst. D, Acta Cryst. E and J. Appl. Cryst.), and has contributed to International Tables for Crystallography (Volume F). Starting with his graduate studies, Sean's career has been devoted to various aspects of structural chemistry and chemical crystallography, including their application in biology and biotechnology. He is an expert in the design, procurement and state-of-the-art application of X-ray diffractometers and crystallographic facilities, and is an experienced teacher of chemical crystallography and crystallographic methods. He is keen to bring new Co-editors on board who will increase the subject, geographical and gender diversity of the Editorial Board, and make it more reflective of Acta Cryst. E’s developing authorship and readership.

The retirement at the end of 2019 of long-standing Section Editor Helen Stoeckli-Evans, to whom we extend our sincere thanks, prompted Professor Díaz de Delgado's appointment. Graciela is already well known to the IUCr as an author (in Acta Cryst. A, Acta Cryst. C and Acta Cryst. E), reviewer, member of the IUCr Executive Committee and Chair of the IUCr Calendar Committee. Her career has been devoted to a wide range of interests in structural chemistry and chemical crystallography, and in the use of single-crystal and powder diffraction for the characterisation of materials. Of particular note are her interests in active pharmaceutical compounds and their application, as well as in natural products isolated from medicinal plants of the Venezuelan Andes. She is determined to encourage submissions from Latin America and the southern hemisphere in general, and to help potential authors, especially graduate students and postdocs, overcome the obstacles (such as structure validation issues) that may prevent them from submitting an interesting manuscript to Acta Cryst. E.

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Commentary

17 Mar 2020
Mirolysin structures open a window on gum disease
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Mirolysin structures open a window on gum disease

Evette S. Radisky

Figure 1. Structure of promirolysin reveals how the pro-segment inhibits enzyme activity prior to proteolytic activation. The N-terminal residues of the pro-segment (salmon) occupy the active site cleft of the catalytic domain (gray), with a key cysteine residue coordinating the catalytic zinc ion (purple). This figure was generated using Pymol from the coordinates of PDB structure 6r7v, reported in this issue by Guevara, Rodriguez-Banqueri et al.

Periodontitis, commonly known as gum disease, is a chronic inflammatory disease characterized by dysregulation of the oral microbiota in the subgingival space below the gum line (Hajishengallis, 2015). Healthy gums are compromised by a proliferation of pathogenic anaerobic bacteria, most commonly the triad of Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia. These pathogens release 'virulence factors', molecules that aid their colonization and survival in the subgingival niche and their evasion of the host immune response. Synergistic interactions of the pathogenic microbes with normal oral microbiota lead to a sustained host inflammatory response, degrading periodontal tissues, eroding bone, and ultimately leading to tooth loss. Severe periodontitis affects around 10% of the human population, and health implications are not limited to oral health; the chronic inflammatory conditions precipitated by the disease can extend to systemic manifestations, contributing to risk of cardiovascular and respiratory diseases, diabetes, rheumatoid arthritis, and cancer (Hajishengallis, 2015; Peters et al., 2017).

Proteases are amongst the most abundant virulence factors produced by periodontal pathogens. These enzymes degrade host proteins to feed bacterial growth, and also serve as key mediators of immune-subversive mechanisms, for example by degrading or inactivating endogenous antimicrobial peptides and components of the host complement system (Hajishengallis, 2015). One of the proteases implicated in these activities is mirolysin, a metalloprotease secreted by T. forsythia. Mirolysin cleaves multiple components of the complement pathway to protect the pathogen against complement-mediated killing, and degrades the antimicrobial peptide LL-37, a human host defense peptide secreted by epithelial and immune cells at sites of infection (Jusko et al., 2015; Koneru et al., 2017). As a recently discovered mediator of T. forsythia survival and immune evasion, mirolysin offers a potential therapeutic target, yet until now the structural basis for its latency, activation and substrate specificity has not been defined.

In this issue of IUCrJ, Guevara, Rodriguez-Banqueri et al. report high-resolution crystal structures of promirolysin, defining the mechanism of latency of the precursor protein (Guevara et al., 2020). Like nearly all proteases, mirolysin is first produced as a zymogen, maintained in an inactive state by the presence of an N-terminal extension known as a pro-peptide, pro-segment or pro-domain (Fig. 1). Upon proteolytic cleavage of the pro-segment, the active site of a protease becomes exposed and accessible to substrates. While unified by this common theme, different clans and families of metalloproteases show myriad variations in the details of how latency is maintained and activation subsequently achieved. These variations have been carefully cataloged in over 60 crystal structures of metalloprotease zymogens, including many from the Gomis-Rüth research group (Arolas et al., 2018). Here, the group finds that the mechanism of latency of promirolysin closely resembles the cysteine switch mechanism of matrix metalloproteinases (MMPs) and a number of other zinc metallopeptidases (Morgunova et al., 1999; Arolas et al., 2018). A stretch of the pro-segment occupies the enzyme active site cleft in an orientation opposite to that of a productively bound substrate, positioning a conserved cysteine residue to bind the catalytic zinc. The cysteine side chain displaces the normally bound water molecule that plays the essential hydrolytic role in proteolysis, thus rendering the zymogen inactive.

While this basic cysteine switch mechanism of latency is well precedented, the promirolysin structure reveals a surprisingly extensive interface between the pro-segment and the catalytic domain. The zymogen structure reveals a buried surface area of 2302 Å² between these structural elements, greater than the average buried surface area for protein–protein complexes, which is remarkable given the small size of the 34-residue pro-segment. The pro-segment and catalytic domain interact through a balance of favorable hydrophobic interactions complemented by an array of hydrogen bonds and salt bridges, the same forces that shape affinity and selectivity of intermolecular protein–protein interactions (Xu et al., 1997). The extensive nature of the broad interface between pro-segment and catalytic domain suggests the possibility that the pro-segment may be capable of inhibiting the enzyme in trans, and serving as a template for engineering protein-based mirolysin inhibitors of therapeutic utility. Similar approaches have shown promise for engineering therapeutic inhibitors of ADAM family metallopeptidases, based upon their much larger pro-domains (Moss et al., 2007; Wong et al., 2016).

Guevara, Rodriguez-Banqueri et al. further report a high-resolution structure of active mirolysin bound to a peptide product, providing insight into determinants of substrate specificity of the protease (Guevara et al., 2020). A preference of mirolysin for cleavage on the N-terminal side of basic residues (Koneru et al., 2017) is explained by the presence of an aspartate residue positioned to form a salt bridge with the substrate. This aspartate residue is conserved among the pappalysin family of metalloproteases to which mirolysin belongs, suggesting that similar specificity may be typical of the entire family, and that the mirolysin structure can offer a model to understand substrate recognition for the larger family. Additionally, this serendipitously trapped product complex may provide yet another starting point from which active site-targeted mirolysin inhibitors might be developed. A similar serendipitous discovery of a product fragment captured in a crystal structure of MMP-13 recently led to the design of a potent peptidomimetic inhibitor of this metalloprotease (Gall et al., 2019). Together the new structures of mirolysin reported here offer a window from which to understand the function of this protease in gum disease, with a glimpse of how one might inhibit this intriguing target.

References

Arolas, J. L., Goulas, T., Cuppari, A. & Gomis-Rüth, F. X. (2018). Chem. Rev. 118, 5581–5597.

Gall, F. M., Hohl, D., Frasson, D., Wermelinger, T., Mittl, P. R. E., Sievers, M. & Riedl, R. (2019). Angew. Chem. Int. Ed. 58, 4051–4055.

Guevara, T., Rodriguez-Banqueri, A., Ksiazek, M., Potempa, J. & Gomis-Rüth, F. X. (2020). IUCrJ, 7, 18–29.

Hajishengallis, G. (2015). Nat. Rev. Immunol. 15, 30–44.

Jusko, M., Potempa, J., Mizgalska, D., Bielecka, E., Ksiazek, M., Riesbeck, K., Garred, P., Eick, S. & Blom, A. M. (2015). J. Immunol. 195, 2231–2240.

Koneru, L., Ksiazek, M., Waligorska, I., Straczek, A., Lukasik, M., Madej, M., Thøgersen, I. B., Enghild, J. J. & Potempa, J. (2017). Biol. Chem. 398, 395–409.

Morgunova, E., Tuuttila, A., Bergmann, U., Isupov, M., Lindqvist, Y., Schneider, G. & Tryggvason, K. (1999). Science 284, 1667–1670.

Moss, M. L., Bomar, M., Liu, Q., Sage, H., Dempsey, P., Lenhart, P. M., Gillispie, P. A., Stoeck, A., Wildeboer, D., Bartsch, J. W., Palmisano, R. & Zhou, P. (2007). J. Biol. Chem. 282, 35712–35721.

Peters, B. A., Wu, J., Pei, Z., Yang, L., Purdue, M. P., Freedman, N. D., Jacobs, E. J., Gapstur, S. M., Hayes, R. B. & Ahn, J. (2017). Cancer Res. 77, 6777–6787.

Wong, E., Cohen, T., Romi, E., Levin, M., Peleg, Y., Arad, U., Yaron, A., Milla, M. E. & Sagi, I. (2016). Sci. Rep. 6, 35598.

Xu, D., Tsai, C. J. & Nussinov, R. (1997). Protein Eng. 10, 999–1012.

This article was originally published in IUCrJ (2020). 7, 3–4.

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Meeting report

16 Mar 2020
Joint Polish-German Crystallographic Meeting 2020
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Joint Polish-German Crystallographic Meeting 2020

Maria Rutkiewicz

Rolf Hilgenfeld during his plenary talk on how crystallography can fight emerging viruses such as SARS, MERS and COVID-19.

The German Crystallographic Society (DGK) and the Polish Crystallographic Association (PCA) both have long-standing traditions of organizing annual events. However, this year a Joint Polish-German Crystallographic Meeting took place for the first time, gathering over 320 participants in Wrocław, Poland, from 24 to 27 February 2020. The conference chairs, Marek Główka (Lodz, Poland), Marek Wołcyrz (Wrocław, Poland), Susan Schorr (Berlin, Germany) and Udo Heinemann (Berlin, Germany), filled a four-day program with great talks and posters. Multiple scientific sessions were interspersed with plenary talks, which – judging by the attendance – were found interesting by crystallographers from very different disciplines.

Conference chairs and organizing committee members during the welcome session of the Joint Polish-German Crystallographic Meeting 2020.

A measure of an extraordinary plenary talk is whether it can capture the undivided attention of an audience with varying backgrounds and interests. And this is exactly what happened when Rolf Hilgenfeld (Lübeck, Germany) presented his lecture on SARS and MERS viruses with a special focus on the recently emerged SARS-CoV-2 (formerly known as 2019-nCoV). The audience’s interest was initially driven by the timeliness of the topic. However, the story of solving the crystal structures of the SARS-CoV-2 main protease and its potential inhibitors, already tested on cell lines, within just days of the publication of the virus genome was captivating in itself. [The Lübeck team's research has now been published in Science.]

Traditionally, the first day of the meeting was an opportunity for the DGK award winners to be announced. Dieter Fenske (Karlsruhe, Germany) received the Carl Herrmann Medal to acknowledge his life-time achievements, especially for his research in inorganic chemistry and crystallography. The Will Kleber commemorative coin for outstanding scientific contributions went to Robert Dinnebier (Stuttgart, Germany) in recognition of his exceptional achievements in the field of powder diffraction, as well as in the training of young scientists and in the service to the research community.

This year, the Max von Laue Prize for outstanding achievements by young scientists was awarded twice for the third time in its history. Tobias Beck (Hamburg, Germany) was recognized for his work on the development and characterization of novel crystalline bio-hybrid materials, which are composed of combinations of protein container building blocks and inorganic nanoparticles. In addition, Matthias Zschornak (Dresden, Germany) was recognized for his methodical development of resonant X-ray scattering to make orbitals visible and his work on defect migration and separation in oxides under the influence of external fields. Finally, the Waltrude and Friedrich Liebau Prize promoting interdisciplinarity of crystallography was awarded to Julian Voss-Andreae (Portland, OR, USA) for his significant artistic and creative work.

The organizers provided an opportunity for 19 young crystallographers to present their work in the form of lightning talks. The jury decided to award three of them with Best Presentation Awards: Elżbieta Wątor (Kraków, Poland), Bipasha Debnatyh (Dresden, Germany) and Zhenyu Wang (Berlin, Germany).

The laureates of the Best Presentation Awards, Zhenyu Wang, Bipasha Debnatyh and Elżbieta Wątor, with the jury members.

After two sessions with 128 poster presentations, three scientists were honored with Poster Awards: Götz Schuck (Berlin, Germany), Katarzyna Kurpiewska (Kraków, Poland) and Yoshimichi Hagiwara (Kyoto, Japan).

The city of Wrocław, which is a traditional location for Polish crystallography meetings, was a beautiful venue for scientific discussions that lasted long into the night. The conference dinner, organized at the amazing Afrykarium of Wrocław’s zoo, was a perfect ending to the third day of exciting talks and scientific discussions.

Polish and German participants sightseeing after the poster session.

The joint conference – an initiative bringing together crystallographers from two neighboring countries – created a very welcome platform for promoting current research and starting new collaborations.

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Meeting report (IUCr supported)

05 Mar 2020
11th School of the Argentinean Association of Crystallography
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11th School of the Argentinean Association of Crystallography

San Carlos de Bariloche XI AACr School (Year 2019).

The XV Annual Meeting of the Argentinean Association of Crystallography (AACr) was held from 12 to 15 November 2019 in the Centro Atómico Bariloche, San Carlos de Bariloche, Río Negro, Argentina. More than 160 crystallographers from different regions of Argentina and from several other Latin American countries participated in the event. Following the Meeting, the XI School of the AACr was held at the same location from 18 to 22 November. The School addressed two topics in parallel:

Course 1: “Structural and magnetic Rietveld refinement of X-ray and neutron diffraction data”, where 35 students had the opportunity to attend lectures by Juan Rodriguez Carvajal (ILL, Grenoble, France), financed by the Maldacena Program (from Instituto Balseiro, Bariloche, Argentina), and Oscar Fabello (ILL), financed by the IUCr Visiting Professorship scheme (replacing María Teresa Fernández Diaz). In addition, many local organizers (Federico Napolitano, Liliana Mogni, Gabirela Aurelio, Martin Saleta, Dina Tobia and Adriana Serquis) participated in the tutorials and special seminars.

Course 2: “Texture and strain in polycrystalline materials”, which was run by Raúl Bolmaro (IFIR Rosario, Argentina), Javier Santisteban (Argentinian Neutron Beams Laboratory) and Florencia Malamud (Centro Atómico Bariloche).

Students attending a Course 2 lecture.

The Local Organizing Committee obtained financial support from the IUCr, Analytical–Bruker, INBOX–Panalytical, Thermo Fisher and the local funding agency, Ministerio de Ciencia y Tecnología. The event brought together 58 participants (postdocs and PhD, MSc and undergraduate students) of different nationalities: Argentina (46), Colombia (5), Cuba (3), Venezuela (2) and Uruguay (2).

The School program consisted of a 40-hour schedule (20 hours of lectures, 18 hours for experimental and practical tutorial sessions and 2 hours for a final exam). A second practical exam was given to the students, to be completed at home and returned two weeks after the School had finished. This two-step exam was taken by 38 participants who will receive academic credit for their participation in the School.

The students were provided with an anonymous survey to obtain their opinions on different aspects of the School. The large majority of comments were positive, many of them including helpful remarks that will be of valuable help in the organization of future Schools.

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The IUCr Newsletter (ISSN 1067-0696; coden IUC-NEB) is published electronically by the International Union of Crystallography. Feature articles, meeting announcements and reports, information on research or other items of potential interest to crystallographers may be submitted to the Editors at any time. Items will be selected for publication on the basis of suitability, content, style, timeliness and appeal.

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11th School of the Argentinean Association of Crystallography

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newsletter design: Michele Zema, Andrea Sharpe, Peter Strickland, Brian McMahon; newsletter logo design: Michele Zema