Crystallography in the News

June 3, 2019. Amgen has discovered a drug to target a supposedly “undruggable” gene mutation, potentially paving the way for a new cancer treatment. The California-based biotech company presented very early data on its research into drugging the protein made by the KRAS gene — a mutation of which is found in many cancers including lung and colorectal.

June 4, 2019. Stephen Cusack and his research group at EMBL Grenoble have, for the first time, observed different functional states of the influenza virus polymerase as it is actively transcribing. It provides the first characterization of the movements of the polymerase during the so-called nucleotide addition cycle, whereby each successive nucleotide is added to the growing mRNA chain.

June 6, 2019. Rigaku and Merck KGaA, Darmstadt, Germany, have formed a partnership to develop lab consumables based on highly innovative crystalline sponge technology, which determines the absolute chemical structure of organic molecules and enables X-ray crystallography without crystallization of the analyte.

June 7, 2019. Groundbreaking research at the new long-wavelength macromolecular crystallography beamline (I23) at Diamond Light Source has for the first time demonstrated the location of potassium ions in bacterial ribosomes. Little was known of the sites of metal ions that are crucial for their structure and function.

June 10, 2019. Scientists at the Sloan Kettering Institute have combined biochemical and computational methods to visualize how an important cancer-related protein changes shape during a chemical reaction. The results will aid drug design.

June 10, 2019. New research reveals the molecular machinery behind the high-intensity sweetness of the stevia plant. The results could be used to engineer new non-caloric products without the aftertaste that many associate with sweetener marketed as Stevia.

June 11, 2019. Small molecule JH-RE-06 was developed by scientists at Duke University and tested in human cancer cell lines and a mouse model of human melanoma. JH-RE-06, which exploits a pair of half pockets that form a whole pocket when two TLS proteins combine, helps preserve the effectiveness of several forms of chemotherapy while also suppressing the ability of cultured cancer cells to mutate in the presence of DNA-damaging drugs.

June 17, 2019. In a scientific first, scientists in the Blavatnik Institute at Harvard Medical School have shown it is possible to determine the 3-D structures of a gene by assessing the effects of lab-made genetic mutations on protein functions. The team's findings represent a significant step toward linking sequence data with its function in cells. The tool is freely available at GitHub.

June 18, 2019. C. trachomatis pathogenicity relies on the creation of an intracellular parasitic niche called an “inclusion,” which is made from the outer membrane of the host cell. When a human cell is infected with multiple Chlamydia, each bacterium will develop an individual inclusion, all of which will ultimately fuse together into one large inclusion. This unique fusion event depends on the chlamydial protein IncA. Microbiologist Fabienne Paumet teamed up with biochemist Gino Cingolani to determine an electron density map of the fusion protein.

June 19, 2019. Researchers have developed a technology to analyze the adsorption behavior of molecules in each individual pore of a metal organic framework (MOF). This system has large specific surface areas, allowing for the real-time observation of the adsorption process of an MOF.

June 19, 2019. Using neutrons to collect structural information on RNA and DNA is no ordinary feat. Small biomolecular samples in dilute solutions often produce noisy scattering patterns, making the data difficult to analyze. Oak Ridge National Laboratory's Bio-SANS detector at the High Flux Isotope Reactor is one of few neutron instruments in the world with the capability to capture small and wide scattering angles simultaneously, combining both global- and local-scale details

June 19, 2019. Memorial Sloan Kettering cancer biologist Michael Kharas's team reported that they have identified a molecule that appears to block the function of Musashi-2, a protein that plays a role in making cancer grow and spread. SKI computational chemist John Chodera, SKI structural biologist Dinshaw Patel, and Yehuda Goldgur, Head of MSK's X-Ray Crystallography Core Facility, helped determine the structure of the Musashi-2 protein and how Ro 08-2750 binds to it. SKI computational biologist Christina Leslie helped with the gene expression data generated from this research.

Product Spotlight

The XtalCheck System

The XtalCheck system is an automated tool for performing in situ crystallography experiments on your existing X-ray diffraction system. Protein crystallography often requires screening large numbers of crystals to identify samples that are suitable for X-ray diffraction experiments. Specifically, crystallographers usually loop and cryo-freeze samples for X-ray screening to identify whether the sample contains a protein or salt and to evaluate diffraction resolution, mosaicity and other crystal parameters. This iterative process of mounting and screening of many samples is time consuming and rarely automated. The XtalCheck system addresses this bottleneck by automating diffraction data collection for crystals directly from SBS format crystallization plates.

The XtalCheck system includes software that facilitates both visual and diffraction imaging of crystallization experiments. With the XtalCheck system, one can easily survey many crystallization experiments by eliminating the need to harvest and cryo-cool samples. Moreover, one can perform serial crystallography experiments, by collecting data from multiple crystals, to achieve complete data sets that can be used for structure solution.

Features:

• Quickly survey crystals prior to cryo-cooling
• Simple queuing of crystal objects for diffraction screening
• Data collection for sample queue progresses without user intervention
• Assign multiple crystal objects per drop

Lab in the Spotlight

The University of Alabama-Tuscaloosa

The University of Alabama-Tuscaloosa recently took delivery of an XtaLAB Synergy-DW Cu/Mo, the first in the Western Hemisphere. Scientist Fengrui Qu says “The new instrument is much more powerful in every regard compared to our previous (aged) instrument. It cuts down the collection time dramatically, to roughly one fourth.” Dr. Qu likes the “What Is This” (WIT) utility, which can provide a connectivity model in just a few minutes. While not good enough for publication, a WIT structure provides sufficient information to allow researchers to decide whether to collect a full data set if the material is interesting. Dr. Qu adds “This feature is very neat, esp. for some synthetic labs. We can use it as a walkup instrument (as NMR) in some cases.” Furthermore, the instrument will also be used for diffuse scattering experiments on molecules and materials and for solving the structure of proteins and other large biomolecules. Beyond UA, it is a resource for regional colleges and universities and it will also be used heavily in teaching. Dr. Fengrui Qu (crystallographer), Dr. Elizabeth Papish (PI), Dr. Jared Allred (co-PI), Dr. Jack Dunkle (co-PI), Dr. Paul Rupar (co-PI), and Dr. Kevin Shaughnessy (co-PI) thank NSF CHE MRI 1828078 and UA for the purchase of the single crystal X-ray diffraction instrument.

Useful Link

AAAS Member Community

AAAS has a central website for all members and member communities (sections) with blogs, events, news and other useful information. You use your AAAS ID to sign in and you can participate in discussions with the greater AAAS membership, as well as the three sections to which you belong. You can also view activities in the 25 other sections. I have just begun to scratch the surface but this seems like a wealth of useful information.

Michael G. Rossmann (1930–2019), pioneer in macromolecular and virus crystallography: scientist, mentor and friend. Arnold, Eddy; Wu, Hao; Johnson, John E. Acta Crystallographica: Section D, Structural Biology. Jun2019, Vol. 75 Issue 6, p523-527. 5p. DOI: 10.1107/S2059798319008398.

HKLF5Tools: a program for processing diffraction data of non-merohedrally twinned crystals. Ivlev, Sergei I.; Conrad, Matthias; Kraus, Florian. Zeitschrift für Kristallographie. Crystalline Materials. Jun2019, Vol. 234 Issue 6, p415-418. 4p. DOI: 10.1515/zkri-2018-2147.

A new crystal structure and small-angle X-ray scattering analysis of the homodimer of human SFPQ. Hewage, Thushara Welwelwela; Caria, Sofia; Lee, Mihwa. Acta Crystallographica: Section F, Structural Biology Communications. Jun2019, Vol. 75 Issue 6, p439-449. 11p. DOI: 10.1107/S2053230X19006599.

Structural Basis for YjbH Adaptor-Mediated Recognition of Transcription Factor Spx. Awad, Wael; Al-Eryani, Yusra; Ekström, Simon; Logan, Derek T.; von Wachenfeldt, Claes. Structure. Jun2019, Vol. 27 Issue 6, p923-923. 1p. DOI: 10.1016/j.str.2019.03.009.

Atypical Lone Pair–π Interaction with Quinone Methides in a Series of Imido-Ferrociphenol Anticancer Drug Candidates. Wang, Yong; Pigeon, Pascal; Top, Siden; Sanz García, Juan; Troufflard, Claire; Ciofini, Ilaria; McGlinchey, Michael J.; Jaouen, Gérard. Angewandte Chemie. 6/17/2019, Vol. 131 Issue 25, p8509-8513. 5p. DOI: 10.1002/ange.201902456.

Laue diffraction and time-resolved crystallography: a personal history. Moffat, Keith. Philosophical Transactions of the Royal Society A: Mathematical, Physical & Engineering Sciences. 6/17/2019, Vol. 377 Issue 2147, p1-10. 10p. DOI: 10.1098/rsta.2018.0243.

Light-Controlled Conformational Switch of an Aromatic Oligoamide Foldamer. Gole, Bappaditya; Kauffmann, Brice; Maurizot, Victor; Huc, Ivan; Ferrand, Yann. Angewandte Chemie International Edition. 6/11/2019, Vol. 58 Issue 24, p8063-8067. 5p. DOI: 10.1002/anie.201902378.

P-Aminophosphaalkenes with C-Isopropyldimethylsilyl Groups. Bîrzoi, Roxana M.; Jones, Peter G.; Bartsch, Rainer; Mont, Wolf-W. Zeitschrift für Anorganische und Allgemeine Chemie. 6/3/2019, Vol. 645 Issue 10, p712-722. 11p. DOI: 10.1002/zaac.201900049.

Synthesis and crystal structures of chiral ferrocene and ruthenocene substituted aminomethylnaphthols obtained through Betti-condensation. Dikova, Krasimira; Kostova, Kalina; Simova, Svetlana; Linden, Anthony; Chimov, Angel; Dimitrov, Vladimir. Polyhedron. Jun2019, Vol. 165, p177-187. 11p. DOI: 10.1016/j.poly.2019.03.019.

Solid State Structure of cis-[W(CO)₄(pip)(PPh₃)]. Harkreader, Jennifer L.; Frost, Brian J. Journal of Chemical Crystallography. Jun2019, Vol. 49 Issue 2, p125-129. 5p. DOI: 10.1007/s10870-018-0743-1.

Koanolide A, antiproliferative germacrane-type sesquiterpene lactone from Koanophyllon gibbosum. Castillo, Quírico A.; Padrón, José M.; Wojtas, Lukasz; Keramane, Mehdi; Germosén, Evelyn A. Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry. Jun2019, Vol. 60 Issue 25, p1640-1642. 3p. DOI: 10.1016/j.tetlet.2019.05.036.

Characteristics of twins in Li(Ni_0.67Co_0.33)O₂ as a cathode material for lithium-ion batteries. Ai, YanLing; Zhang, M.Q.; Jiang, F.; Zhang, Ruizhi; Liu, Jun.; Wang, C.; Xiao, W.H. Journal of Alloys & Compounds. Jun2019, Vol. 791, p1167-1175. 9p. DOI: 10.1016/j.jallcom.2019.03.376.

Protein encapsulation in the hollow space of hemocyanin crystals containing a covalently conjugated ligand. Hashimoto, Tsubasa; Ye, Yuxin; Ui, Mihoko; Ogawa, Tomohisa; Matsui, Takashi; Tanaka, Yoshikazu. Biochemical & Biophysical Research Communications. Jun2019, Vol. 514 Issue 1, p31-36. 6p. DOI: 10.1016/j.bbrc.2019.04.062.

Structure, Hirshfeld surface and theoretical study of a new inorganic organic arsenate compound NaH₂AsO₄·(C₁₂H₈N₂)·1.5H₂O. Harchani, Ali; Kaminsky, Werner; Haddad, Amor. Journal of Molecular Structure. Jun2019, Vol. 1186, p60-67. 8p. DOI: 10.1016/j.molstruc.2019.03.018.

Half-sandwich Ni(II) complexes [Ni(Cp)(X)(NHC)]: From an underestimated discovery to a new chapter in organonickel chemistry. Banach, L.; Gunka, P.A.; Zachara, J.; Buchowicz, W. Coordination Chemistry Reviews. Jun2019, Vol. 389, p19-58. 40p. DOI: 10.1016/j.ccr.2019.03.006.

A Microporous Metal-Organic Framework Supramolecularly Assembled from a Cu^II Dodecaborate Cluster Complex for Selective Gas Separation. Zhang, Yuanbin; Yang, Lifeng; Wang, Lingyao; Duttwyler, Simon; Xing, Huabin. Angewandte Chemie International Edition. 6/11/2019, Vol. 58 Issue 24, p8145-8150. 6p. DOI: 10.1002/anie.201903600.

Accurate and efficient representation of intramolecular energy in ab initio generation of crystal structures. II. Smoothed intramolecular potentials. Sugden, Isaac J.; Adjiman, Claire S.; Pantelides, Constantinos C. Acta Crystallographica: Section B, Structural Science, Crystal Engineering & Materials. Jun2019, Vol. 75 Issue 3, p423-433. 11p. DOI: 10.1107/S2052520619005778.

Effect of water of crystallization on aggregation-induced emission in structurally similar crystals. Hayashi, Naoto; Okamoto, Naoki; Onoue, Masaya; Yamamoto, Kensuke; Yoshino, Junro. Tetrahedron Letters: International Organ for the Rapid Publication of Preliminary Communications in Organic Chemistry. Jun2019, Vol. 60 Issue 25, p1663-1666. 4p. DOI: 10.1016/j.tetlet.2019.05.040.

Structural basis for efonidipine block of a voltage-gated Ca²⁺ channel. Xu, Fuyan; Xiong, Weixi; Huang, Yiman; Shen, Jianghua; Zhou, Dong; Tang, Lin. Biochemical & Biophysical Research Communications. Jun2019, Vol. 513 Issue 3, p631-634. 4p. DOI: 10.1016/j.bbrc.2019.03.176.

Zinc-oxaprozin compounds: Synthesis, structure and biological activity. Lazou, Marialena; Hatzidimitriou, Antonios G.; Papadopoulos, Athanasios N.; Psomas, George. Journal of Inorganic Biochemistry. Jun2019, Vol. 195, p101-110. 10p. DOI: 10.1016/j.jinorgbio.2019.03.016.

Probing the antibacterial and anticancer potential of tryptamine based mixed ligand Schiff base Ruthenium(III) complexes. Malik, Manzoor Ahmad; Raza, Md Kausar; Dar, Ovas Ahmad; Amadudin; Abid, Mohammad; Wani, Mohmmad Younus; Al-Bogami, Abdullah Saad; Hashmi, Athar Adil. Bioorganic Chemistry. Jun2019, Vol. 87, p773-782. 10p. DOI: 10.1016/j.bioorg.2019.03.080.

Pyrazolyl-phosphinoyl nickel (II) complexes: synthesis, characterization and ethylene dimerization studies. Junges, C.H.; Dresch, L.C.; Costa, M.T.; Tirloni, B.; Casagrande, O.L.; Stieler, R. Applied Organometallic Chemistry. Jun2019, Vol. 33 Issue 6, pN.PAG-N.PAG. 1p. DOI: 10.1002/aoc.4887.

Book Review

The Universe Speaks in Numbers: How Modern Math Reveals Nature's Deepest Secrets
By Graham Farmelo, ISBN: 978-0-465-05665-1

In The Universe Speaks in Numbers, Graham Farmelo presents a concise version of the history of the relationship between mathematics and physics. As Farmelo explains in his book, the relationship, though perhaps a natural one, has not always been an easy one. He even goes so far as to describe it as one that has gone through a long divorce and subsequent reconciliation.

Farmelo begins by describing Einstein's philosophy, that a purely mathematical and theoretical approach to the study of physics could wield meaningful insights into the natural world, as opposed to a purely experimental one. Even though Einstein's genius was celebrated in his own time as it is now, such an approach was considered laughable by many of his peers and fellow physicists. A young Robert Oppenheimer once described Einstein as “completely cuckoo,” Farmelo explains. And Oppenheimer wasn't the only one.

But, as with many great minds, Einstein was simply ahead of his time. A significant amount of scientific research up to that point was observation- and experiment-based. Now, the use of mathematics to study and describe physics on a theoretical level is widely practiced—string theory comes to mind as perhaps the most famous example of theoretical physics in the forefront of the zeitgeist.

After beginning with Einstein, Farmelo goes back to the basics—classical physics. It's a field that Isaac Newton—a mathematician by practice and title—helped describe. Newton, despite being well-known in high school and college physics courses today for his Laws of Motion, would not have considered himself a physicist in his own time. Newton described his use of mathematics to explain what he saw in nature in his Principia—now considered a foundational text of calculus. Today, calculus and physics are essentially married subjects—but, in Newton's time, the idea of wedding mathematical calculations with experimental insights to support theoretical observations was revolutionary, to say the least. His work catalyzed the integrated study of mathematics and science in an unprecedented way that would culminate in the invention of modern physics in the twentieth century.

Farmelo makes sure to pay his respects to some of Newton's “giant” predecessors, upon whose shoulders Newton stood to see further. These include Aristotle and Galileo, amongst others. But the main focus of Farmelo's first chapter is Newton. After Newton, he details James Clerk Maxwell's mathematical investigations into electromagnetism—the culmination of which is a series of equations that bear his name. From there, Farmelo moves on to the two revolutionary discoveries that define modern physics: basic relativity and quantum mechanics.

Then, Farmelo comes to the aforementioned long divorce. In the mid-twentieth century, many physicists, Freeman Dyson among them, felt physics stood alone from mathematics. Experimentation and observation were the foundations of the field. Dyson and his fellow physicists viewed the mathematical foundations of theoretical physics with skepticism. Now 92, Dyson—along with others in the field—have changed their tune. It's intriguing to read The Universe Speaks in Numbers not long after reading Dyson’s memoir Maker of Patterns: An Autobiography through Letters. He's gone from being the narrator to the narrated, so to speak—from the director of the show to an actor in it, and it's an interesting transition. If you want more on Dyson after reading The Universe Speaks in Numbers, or even if you want a scientist's immediate perspective on the events Farmelo describes in his own book, I recommend checking out Dyson's memoir. [A review of Maker of Patterns will appear here next month – JDF]

It's humbling to note, as Farmelo does, that it took three centuries to get from Newton to the Standard Model of particle physics, and only four decades to get from the Standard Model to where we are today. The last four decades occupy the second half of The Universe Speaks in Numbers and, as you might expect, more modern characters like Stephen Hawking make an appearance, while Dyson continues to pop up as the fields of theoretical physics and mathematics begin to repair their relationship and reconcile. If you want to learn how, you’ll have to read it for yourself.

Farmelo is both a professor of physics and a skilled science writer—and it shows. He demonstrates a firm command of the subject matter, which coupled with his accessible language and writing style makes The Universe Speaks in Numbers a delightful and insightful read.

Review by Jeanette S. Ferrara, MA