Rigaku Symposium on X-ray Diffraction

The Rigaku Symposium on X-ray Diffraction is an annual event hosted at Yale University that is free to the public. The symposium features interactive workshops with tutorials on X-ray characterization for macromolecular, small molecule and materials projects. The 5th Rigaku Symposium on X-ray Diffraction took place at Yale University Department of Chemistry May 19th and 20th.

ROD was represented by Joe Ferrara, Pierre Le Magueres, and Eric Reinheimer. The morning of May 19th, Pierre ran a BioSAXS workshop and Joe and Eric ran the single crystal workshops in the afternoon. Friday was dedicated to scientific presentations followed by a poster session and dinner.

Crystallography in the news

June 1, 2016. The Blavatnik National Awards for Young Scientists announced today the 31 National Finalists who will be competing for three spots as the 2016 Blavatnik National Laureates. The Finalists were selected from 308 nominations of outstanding faculty-rank researchers from 148 of the nation's leading academic and research institutions.

June 4, 2016. Pathogen-specific antibiotics will help minimize the harm caused to the "good bacteria" in the human microbiome, and in turn, result in a more effective cure for illnesses caused by bacteria and a lower amount of antibiotic resistance, said Nobel Laureate Professor Ada E. Yonath, who delivered the 8th JBS Haldane Lecture at KIIT University in Odisha capital today.

June 6, 2016. Researchers at Florida Atlantic University have engineered endogenous protein inhibitors of protein-degrading enzymes as an alternative approach to synthetic inhibitors for potentially treating cancer and other diseases.

June 9, 2016. This spring, Caltech students had the opportunity to use X-ray crystallography to solve protein structures themselves in a new course taught by Professor of Chemistry André Hoelz.

June 10, 2016. Professor Xiaodong Zhang has been elected to membership of the European Molecular Biology Organisation (EMBO). Zhang is Professor of Macromolecular Structure and Function from the Department of Medicine at Imperial, where her work focuses on unravelling the mechanisms of molecular machines using a range of techniques including X-ray crystallography and cryo-electron microscopy.

June 10, 2016. Keene State College's first ever teaching post-doctoral fellow, Dr. Manpreet Kaur, arrived on campus from Mysore, India in early May and got right to work in the Single Crystal X-ray Crystallography lab with chemistry professor Dr. Jerry Jasinski, who conducts research that describes the molecular structure of substances which often leads to the development of new pharmaceutical products.

June 13, 2016. The Burroughs Wellcome Fund has awarded Emory biochemist Christine Dunham, PhD, $500,000 over five years to investigate how some bacteria withstand antibiotic treatment. Her research aims to dissect the functions of bacterial proteins that regulate "persistence," a non-replicating antibiotic-tolerant state that may cause unexplained treatment failures in the clinic.

June 13, 2016. Caltech's Paul Asimow and his co-authors describe how subjecting certain rare materials to extremely strong shock waves produces quasicrystals. Their results suggest that quasicrystals may form in rocky bodies during collisions in the asteroid belt, before falling to earth as meteorites.

June 13, 2016. Dr. Francesca Fabbiani, chemist at the University of Göttingen, has received the Max von Laue Award of the German Crystallographic Society (DGK). With the award, the DGK honors Dr. Fabbiani's contribution to the field of high-pressure crystallography on pharmaceuticals.

June 13, 2016. Introducing graphene into microfluidic devices can make it easier to study proteins at an atomic level, scientists in the US have shown. Devices that are thinner and interfere less with the measurements allow larger and more intricate protein structures to be resolved using techniques that rely on probing thousands of microcrystals.

June 16, 2016. Richard Henderson,a molecular biologist and biophysicist and group leader in the structural studies division at the Medical Research Council Laboratory of Molecular Biology, University of Cambridge, was announced as the winner of the Royal Society-awarded Copley Medal, the world's oldest scientific prize.

June 20, 2016. Prof Rajni Kant of Physics and Chief-Coordinator Offsite Campuses, University of Jammu, has been selected to prestigious National Academy of Sciences India (NASI) as its Member. Prof Rajni Kant was recently selected to the International Council for Science Unions (ICSU) as a member of the select committee for International Union of Crystallography-Indian National Science Academy (IUCr-INSA) supported National Committee on Crystallography for a period of four years.

June 22, 2016. "The all-or-nothing nature of crystallographic structure determination projects aggravates a systemic problem caused by increasingly risk-adverse funding policies. Additionally, the unprecedented progress in targeted molecular biology and protein biochemistry methods, and crystallographic techniques, appears widely under appreciated. As I discuss here, historically rooted and outdated grant review criteria need urgent revision." – Bernhard Rupp, Ph.D.

Product spotlight: MIPs – molecularly imprinted polymers

Polymer-based nucleating agents enhance the diffraction resolution in the home lab

Prof. Naomi Chayen, Professor of Biomedical Sciences at Imperial College, UK, reports the use of smart, polymer-based nucleating agents that enable Human macrophage migration inhibitory factor to diffract X-rays to a resolution of 1.2 Å using a home lab Rigaku MicroMax-007 HFM X-ray generator.

The MicroMax-007 HF is the most widely used home lab X-ray source for protein crystallography and a popular source for small molecule crystallographers who need the additional flux of a rotating anode generator. The ability to achieve such high resolution using a home lab X-ray source is extremely powerful, and opens the door for researchers to investigate complex biomolecules without the need for synchrotron radiation.

The successful nucleating agents are MIPs – molecularly imprinted polymers – which can be imprinted with molecules of the protein under investigation to produce a 'mould' of the protein. Moreover, A MIP template of one protein can also act as a nucleating agent for other proteins of similar molecular weight. Chayen and colleagues have successfully grown diffraction quality crystals of a range of proteins including an HIV complex and a complex of an antibody with a fragment of the CCR5 receptor and have demonstrated the MIPs use in automated crystallisation robots. MIPs can be purchased through Imperial Innovations' Quicktech website.

A typical crystal of human macrophage migration inhibitory factor (MIF)
crystallised in the presence of MIP

Lab in the spotlight

Professor Naomi Chayen
Faculty of Medicine, Department of Surgery & Cancer
Prof Res Fellow – Professor of Biomedical Sciences
Imperial College London

Naomi E. Chayen is Professor of Biomedical Sciences at Imperial College London and the Head of the crystallization group in Computational and Systems Medicine. She specializes in the crystallization of proteins and other biological macromolecules, in particular, developing a fundamental understanding of the crystallization process and exploiting this to design practical methodology (including high-throughput methods) for producing high quality crystals of medical and industrial interest. Naomi has developed many unique methods adopted by crystal growth laboratories worldwide, several of which are commercialized (recently Naomi's Nucleant; Chayen Reddy MIP). Her methods have resulted in successful crystallization, leading to the structure determination of numerous proteins including membrane proteins and large macromolecular complexes that had previously failed to crystallize using conventional techniques. She has received several awards among them an Innovator of the Year Prize and Women of Outstanding Achievement for Innovation and Entrepreneurship commendation.

Visit Naomi's page at Imperial College London

Useful link: Crystallographic Web Applets

Following links from Bernhard Rupp's tutorial web site to Amazon.com allows you to find the best new and used prices on crystallography books along with his recommendations.

SUNBIM: a package for X-ray imaging of nano- and biomaterials using SAXS, WAXS, GISAXS and GIWAXS techniques. Siliqi, Dritan; De Caro, Liberato; Ladisa, Massimo; Scattarella, Francesco; Mazzone, Annamaria; Altamura, Davide; Sibillano, Teresa; Giannini, Cinzia. Journal of Applied Crystallography. Jun2016, Vol. 49 Issue 3, p1107-1114. 7p. DOI: 10.1107/S1600576716006932.

On the influence of crystal size and wavelength on native SAD phasing. Liebschner, Dorothee; Yamada, Yusuke; Matsugaki, Naohiro; Senda, Miki; Senda, Toshiya. Acta Crystallographica Section D: Structural Biology. Jun2016, Vol. 72 Issue 6, p728-741. 13p. DOI: 10.1107/S2059798316005349.

The first synthesis and X-ray crystallographic analysis of an oxygen-bridged planarized triphenylborane. Kitamoto, Yuichi; Suzuki, Takatsugu; Miyata, Yasuo; Kita, Hiroshi; Funaki, Kenji; Oi, Shuichi. Chemical Communications. 6/4/2016, Vol. 52 Issue 44, p7098-7101. 4p. DOI: 10.1039/c6cc02440h.

X-ray Crystallographic Structure of Thermophilic Rhodopsin. Takashi Tsukamoto; Kenji Mizutani; Taisuke Hasegawa; Megumi Takahashi; Naoya Honda; Naoki Hashimoto; Kazumi Shimono; Keitaro Yamashita; Shigehiko Hayashi; Takeshi Murata; Yuki Sudo. Journal of Biological Chemistry. 6/3/2016, Vol. 291 Issue 23, p12223-12232. 10p. DOI: 10.1074/jbc.M116.719815.

Identification of rogue datasets in serial crystallography. Assmann, Greta; Brehm, Wolfgang; Diederichs, Kay. Journal of Applied Crystallography. Jun2016, Vol. 49 Issue 3, p1021-1028. 7p. DOI: 10.1107/S1600576716005471.

Room-temperature macromolecular crystallography using a micro-patterned silicon chip with minimal background scattering. Roedig, Philip; Duman, Ramona; Sanchez-Weatherby, Juan; Vartiainen, Ismo; Burkhardt, Anja; Warmer, Martin; David, Christian; Wagner, Armin; Meents, Alke. Journal of Applied Crystallography. Jun2016, Vol. 49 Issue 3, p968-975. 7p. DOI: 10.1107/S1600576716006348.

Novel protein-inhibitor interactions in site 3 of Ca²⁺-bound S100B as discovered by X-ray crystallography. Cavalier, Michael C.; Melville, Zephan; Aligholizadeh, Ehson; Raman, E. Prabhu; Yu, Wenbo; Fang, Lei; Alasady, Milad; Pierce, Adam D.; Wilder, Paul T.; MacKerell, Alexander D.; Weber, David J. Acta Crystallographica Section D: Structural Biology. Jun2016, Vol. 72 Issue 6, p753-760. 7p. DOI: 10.1107/S2059798316005532.

OnDA: online data analysis and feedback for serial X-ray imaging. Mariani, Valerio; Morgan, Andrew; Yoon, Chun Hong; Lane, Thomas J.; White, Thomas A.; O'Grady, Christopher; Kuhn, Manuela; Aplin, Steve; Koglin, Jason; Barty, Anton; Chapman, Henry N. Journal of Applied Crystallography. Jun2016, Vol. 49 Issue 3, p1073-1080. 7p. DOI: 10.1107/S1600576716007469.

DNA polymorphism in crystals: three stable conformations for the decadeoxynucleotide d(GCATGCATGC). Thirugnanasambandam, Arunachalam; Karthik, Selvam; Artheswari, Gunanithi; Gautham, Namasivayam. Acta Crystallographica Section D: Structural Biology. Jun2016, Vol. 72 Issue 6, p780-788. 8p. DOI: 10.1107/S2059798316006306.

Predicting Allosteric Effects from Orthosteric Binding in Hsp90-Ligand Interactions: Implications for Fragment-Based Drug Design. Chandramohan, Arun; Krishnamurthy, Srinath; Larsson, Andreas; Nordlund, Paer; Jansson, Anna; Anand, Ganesh S. PLoS Computational Biology. 6/2/2016, Vol. 12 Issue 6, p1-17. 17p. DOI: 10.1371/journal.pcbi.1004840.

4-Aminoquinaldine monohydrate polymorphism: prediction and impurity aided discovery of a difficult to access stable form. Braun, Doris E.; Oberacher, Herbert; Arnhard, Kathrin; Orlova, Maria; Griesser, Ulrich J. CrystEngComm. 6/14/2016, Vol. 18 Issue 22, p4053-4067. 15p. DOI: 10.1039/c5ce01758k.

Anisotropic compressibility of the coordination polymer emim[Mn(btc)]. Madsen, Solveig R.; Moggach, Stephen A.; Overgaard, Jacob; Brummerstedt Iversen, Bo. Acta Crystallographica: Section B, Structural Science, Crystal Engineering & Materials. Jun2016, Vol. 72 Issue 3, p389-394. 5p. DOI: 10.1107/S2052520616005515.

Overcoming bottlenecks in the membrane protein structural biology pipeline. Hardy, David; Bill, Roslyn M.; Jawhari, Anass; Rothnie, Alice J. Biochemical Society Transactions. Jun2016, Vol. 44 Issue 3, p838-844. 7p. DOI: 10.1042/BST20160049.

The crystal structure of Escherichia coli CsdE. Kenne, Adela N.; Kim, Sunmin; Park, SangYoun. International Journal of Biological Macromolecules. Jun2016, Vol. 87, p317-321. 5p. DOI: 10.1016/j.ijbiomac.2016.02.071.

Quantifying radiation damage in biomolecular small-angle X-ray scattering. Hopkins, Jesse B.; Thorne, Robert E. Journal of Applied Crystallography. Jun2016, Vol. 49 Issue 3, p880-890. 10p. DOI: 10.1107/S1600576716005136.

The first crystal structure of human RNase 6 reveals a novel substrate-binding and cleavage site arrangement. Prats-Ejarque, Guillem; Arranz-Trullén, Javier; Blanco, Jose A.; Pulido, David; Victòria Nogués, M.; Moussaoui, Mohammed; Boix, Ester. Biochemical Journal. 6/1/2016, Vol. 473 Issue 11, p1523-1536. 14p. DOI: 10.1042/BCJ20160245.

Triethylammonium salt of dimethyl diphenyldithiophosphates: Single crystal X-ray and DFT analysis. Kumar, Sandeep; Khajuria, Ruchi; Kour, Mandeep; Kumar, Rakesh; Rana, Love; Hundal, Geeta; Gupta, Vivek; Kant, Rajni; Pandey, Sushil. Journal of Chemical Sciences. Jun2016, Vol. 128 Issue 6, p921-928. 8p. DOI: 10.1007/s12039-016-1083-3.

Atomic Structure and Biochemical Characterization of an RNA Endonuclease in the N Terminus of Andes Virus L Protein. Fernández-García, Yaiza; Reguera, Juan; Busch, Carola; Witte, Gregor; Sánchez-Ramos, Oliberto; Betzel, Christian; Cusack, Stephen; Günther, Stephan; Reindl, Sophia. PLoS Pathogens. 6/14/2016, Vol. 14 Issue 6, p1-18. 18p. DOI: 10.1371/journal.ppat.1005635.

Crystallographic studies of the complex of human HINT1 protein with a non-hydrolyzable analog of Ap₄A. Dolot, Rafal; Kaczmarek, Renata; Seda, Aleksandra; Krakowiak, Agnieszka; Baraniak, Janina; Nawrot, Barbara. International Journal of Biological Macromolecules. Jun2016, Vol. 87, p62-69. 8p. DOI: 10.1016/j.ijbiomac.2016.02.047.

Allostery: An Overview of Its History, Concepts, Methods, and Applications. Liu, Jin; Nussinov, Ruth. PLoS Computational Biology. 6/2/2016, Vol. 12 Issue 6, p1-5. 5p. DOI: 10.1371/journal.pcbi.1004966.

Bending-Twisting Motions and Main Interactions in Nucleoplasmin Nuclear Import. Geraldo, Marcos Tadeu; Takeda, Agnes Alessandra Sekijima; Braz, Antônio Sérgio Kimus; Lemke, Ney. PLoS ONE. 6/3/2016, Vol. 11 Issue 6, p1-21. 21p. DOI: 10.1371/journal.pone.0157162.

Book review:

Structural DNA Nanotechnology  by Nadrian C. Seeman, Cambridge University Press, Cambridge, 2015, 266 pages, ISBN: 978-0521764483.

Nadrian C. Seeman has been at New York University since 1988, but wrote most of the book while on sabbatical in 2011 in San Francisco. Seeman is the founder of the field of DNA nanotechnology and has been given a number of awards, including the Feynman and Kavli Prizes, in recognition of his groundbreaking work. Seeman comments that he came up with the idea of making nanoscale structures with DNA in a bar in 1980, but he doesn't elaborate. I would have enjoyed the rest of that story.

The book has 14 chapters. The first four cover the origin of the title topic: DNA nanotechnology. The most important statement in chapter 1 is actually in the caption of Figure 1-8: "the central concept of structural DNA nanotechnology: combining branched junctions into larger constructs." This statement captures the crux of the science Seeman describes throughout the whole book. The next two chapters cover the design of sequences to generate branched junctions and motifs by reciprocal exchange. Here a diagrammatical notation is introduced to display complex structures. This notation is further refined in chapter 4, which covers SS DNA topology, starting with knots and nodes and ending with complicated constructs.

Chapter 5 moves from the theoretical to the practical side and describes how to start building and characterizing DNA nanostructures, mostly through FRET and AFM, but occasionally through X-ray crystallography. Chapter 6 looks at robust motifs, essential for building DNA nanostructures. The next two chapters look at making larger structures and mechanical devices from the basic building junctions and motifs, with the latter chapter ending with a discussion on a (very cool) nano-scale bipedal walker.

Chapter 9 covers the topic of origami, things you can make through folding, and bricks, the building blocks of even larger structures. Chapter 10 picks up where chapter 8 left off and combines the concepts of structure and motion to produce a nano-assembly line. This provides a good segue into the next chapter – a discussion about self-replicating systems.

Chapter 12 covers the concept of computing with DNA. Seeman gives the example of a simple traveling salesman problem and describing how to implement basic logic functionality with DNA. Chapter 13 covers the concepts of triplex DNA, G-tetrads, the I motif and RNA constructs. The final chapter looks at how DNA constructs can be used to organize other objects.

The book uses a copious number of figures to explain the various concepts and is very well referenced.

We probably won't be seeing as many reviews from Jeanette here anymore. She has started publishing articles and reviews on a weekly basis on the NYU site scienceline.org. Her review of The Gene by Siddhartha Mukherjee, as well an article on the Zika virus, may be found there.

Review by Joseph D. Ferrara, Ph.D.
Chief Science Officer, Rigaku