Crystallography in the News

September 2, 2019. Chemists at the University of Amsterdam have significantly improved the experimental determination of the chirality or "handedness" of molecules using vibrational circular dichroism (VCD) spectroscopy. By employing a genetic algorithm they were able to "tame" the uncertainties in VCD analysis resulting from the fact that flexible molecules can adopt many structural conformations.

September 4, 2019. A report from scientists at the Moscow Institute of Physics and Technology highlights the advantages and disadvantages of serial femtosecond X-ray crystallography. This article investigates the review, focusing on its role in drug development.

September 4, 2019. Using an integrated approach that includes X-ray crystallography, solid- and solution-state nuclear magnetic resonance, molecular dynamics simulations, and isothermal titration calorimetry, researchers showed that the proteasome inhibitor bortezomib binds to the ClpP active-site serine, mimicking a peptide substrate, and induces a concerted allosteric activation of the complex.

September 4, 2019. Using crystallography and cryo-electron microscopy, researchers in the UK determined the structures of FluPolA from human influenza A/NT/60/1968 (H3N2) and avian influenza A/duck/Fujian/01/2002 (H5N1) viruses at a resolution of 3.0–4.3 Å, in the presence or absence of a cRNA or vRNA template

September 5, 2019. An international research team has for the first time determined the atomic structure of a protein kinase called PKG in Plasmodium parasites that cause malaria, a finding that potentially will help create a new generation of anti-malarial drugs and advance fundamental research.

September 6, 2019. Researchers from Oxford University have worked out the molecular structure of a protein that is vital for survival of the flu virus. Recently published in Nature, they used several different techniques to look at the arrangement of atoms within a protein that the human flu virus uses to make new copies of its genetic information.

Sepember 13, 2019. Enzymes often form dimers or higher-order oligomers, even when each active site is isolated and the reactions are simple. But the effect of a neighbor can be profound. Mehrabi et al. used a photolabile compound to initiate a reaction in the enzyme fluoroacetate dehalogenase, which they could follow by time-resolved serial synchrotron crystallography.

September 16, 2019. A new protein crystallography sample holder has been developed by Dr. Manfred Weiss and Dr. Christian Feiler from the MX team together with Dr. Dirk Wallacher from the BESSY II sample environment group. Instead of the traditional approach, the protein solution is applied directly onto the sample holder and crystallised in place, eliminating the need to transfer the delicate protein crystals to a different sample holder for analysis.

September 16, 2019. Researchers from the Institute of Cancer Research in London have made fresh discoveries about the structure and function of DHX8. This is a molecule that plays an important role in alternative splicing, and its activity could help explain how cancer can hijack this vital process and use it for its own benefit.

Product Spotlight

XtaLAB Synergy-R

Rigaku XtaLAB Synergy-R is the most powerful small molecule diffractometer available. It includes a high-flux, low-maintenance microfocus rotating anode, the PhotonJet-R, with a high-precision kappa goniometer and Rigaku's own Hybrid Photon Counting (HPC) X-ray detector the HyPix-6000HE. The PhotonJet-R X-ray source is comprised of a Micromax-007 HF rotating anode and a newly designed optic. It is available with either Cu or Mo anodes.

This single crystal X-ray diffractometer has been specially designed to fully integrate the rotating anode X-ray source with all system components and software making it a sleek, simple to use diffractometer without compromising the X-ray intensity.

For labs with high-throughput requirements, increasing the flux reduces data collection time and thus increases the number of samples that can be studied in your laboratory. For extremely small samples, additional flux will extend the minimum size limits for crystals that you can study.

Benefits:

• Fast workflow due to complete integration of software and hardware
• Excels at the most challenging applications, e.g. MOFs or incommensurate structures
• Extremely high performance due to bright source, noise-free detector and fast goniometer speeds
• Provides unparalleled throughput
• Compact design to fit in your laboratory

Lab in the Spotlight

Kirin Holdings Co., Ltd.

Kirin Holdings Co., Ltd. engages in a wide range of research and development. The Central Laboratories for Key Technologies have a goal of creating and acquiring unique technologies that will provide competitive advantages in the future, looking beyond current activities. This is the "dantotsu" philosophy of Kirin - to be better than the best.

Dr. Yoshimasa Taniguchi, a researcher at Kirin, has chosen a unique way to achieve this goal. Taniguchi-san joined Kirin in 2006 to study the health benefits of hop-related compounds. In order to understand the structure of the compounds in hops that provide flavor and health benefits, he began a sabbatical in the laboratory of Professor Makoto Fujita in the Graduate School of Engineering at The University of Tokyo in 2017.

During his research at The University of Tokyo, Taniguchi-san used the crystalline sponge method (CSM) to determine the absolute structures of trans-isohumulone derived from hops, as well as a number of its transformation products occurring during beer aging. In all, the structure of 13 compounds (representative ones shown below) was determined in a period of 3 months by the CSM. Taniguchi-san has returned to Kirin where he continues his research in hop-related compounds.

Structures of trans-isohumulone and its transformation products determined by the crystalline sponge method.

Useful Links

Here is a trio of useful links provided by the American Crystallographic Association. Note the first two are benefits for members of the ACA.

The first link is a mechanism to let others know you are looking for a job. Go to https://acas.memberclicks.net/my-profile. Edit your profile, scroll down to "Open to Career Opportunities", select "Yes" and save the profile.

The second link is a search button to locate people who are open to career opportunities: https://acas.memberclicks.net/member-directory-mo#/. Once you are logged in as a member, simply click "Yes" to "Open to Career Opportunities" and click "Search".

The last item is a link to the ACA's History Page that is open to everyone: https://history.amercrystalassn.org. For those of you in the ACA, there is a button at the bottom of the page: https://history.amercrystalassn.org/volunteer-for-aca-history, where you can contribute to the History page.

Design of cross-linked RNA/protein complexes for structural studies. Dégut, Clément; Schwarz, Veronika; Ponchon, Luc; Barraud, Pierre; Micura, Ronald; Tisné, Carine. Biochimie. Sep2019, Vol. 164, p95-98. 4p. DOI: 10.1016/j.biochi.2019.03.021.

A systematic comparison of sitting and hanging-drop crystallization using traditional and cross-diffusion microbatch crystallization plates. Hou, Hai; Shi, Miao; Hu, Shan-Yang; Ahmad, Fiaz; Zhang, Bin; Chen, Zhong-Hao; Yin, Da-Chuan. Journal of Crystal Growth. Sep2019, Vol. 521, p1-8. 8p. DOI: 10.1016/j.jcrysgro.2019.05.011.

Induction of rare conformation of oligosaccharide by binding to calcium-dependent bacterial lectin: X-ray crystallography and modelling study. Lepsik, Martin; Sommer, Roman; Kuhaudomlarp, Sakonwan; Lelimousin, Mickaël; Paci, Emanuele; Varrot, Annabelle; Titz, Alexander; Imberty, Anne. European Journal of Medicinal Chemistry. Sep2019, Vol. 177, p212-220. 9p. DOI: 10.1016/j.ejmech.2019.05.049.

Structure determination using solution NMR: Is it worth the effort? Takeuchi, Koh; Baskaran, Kumaran; Arthanari, Haribabu. Journal of Magnetic Resonance. Sep2019, Vol. 306, p195-201. 7p. DOI: 10.1016/j.jmr.2019.07.045.

Cyclopentadienyl ruthenium complexes of mixed heterocyclic thiol and Bis(diphenylphosphino)ferrocene ligands. Alshurafa, Hadil; El-khateeb, Mohammad; Abul-Futouh, Hassan; Görls, Helmar; Weigand, Wolfgang. Journal of Molecular Structure. Sep2019, Vol. 1191, p1-5. 5p. DOI: 10.1016/j.molstruc.2019.04.008.

Reducing sample consumption for serial crystallography using acoustic drop ejection. Davy, Bradley; Axford, Danny; Beale, John H.; Butryn, Agata; Docker, Peter; Ebrahim, Ali; Leen, Gabriel; Orville, Allen M.; Owen, Robin L.; Aller, Pierre. Journal of Synchrotron Radiation. Sep2019, Vol. 26 Issue 5, p1820-1825. 6p. DOI: 10.1107/S1600577519009329.

Identification of a novel orally bioavailable ERK5 inhibitor with selectivity over p38α and BRD4. Myers, Stephanie M.; Miller, Duncan C.; Molyneux, Lauren; Arasta, Mercedes; Bawn, Ruth H.; Blackburn, Timothy J.; Cook, Simon J.; Edwards, Noel; Endicott, Jane A.; Golding, Bernard T.; Griffin, Roger J.; Hammonds, Tim; Hardcastle, Ian R.; Harnor, Suzannah J.; Heptinstall, Amy B.; Lochhead, Pamela A.; Martin, Mathew P.; Martin, Nick C.; Newell, David R.; Owen, Paul J. European Journal of Medicinal Chemistry. Sep2019, Vol. 178, p530-543. 14p. DOI: 10.1016/j.ejmech.2019.05.057.

Synthesis and redox chemistry of Pd(II) complexes of a pincer verdazyl ligand. Sanz, Corey A.; Patrick, Brian O.; Hicks, Robin G. Dalton Transactions: An International Journal of Inorganic Chemistry. 9/7/2019, Vol. 48 Issue 33, p12674-12683. 10p. DOI: 10.1039/c9dt02549a.

Removal and recovery of iodide by using a new metal-organic framework based on mixed tetrazolate and carboxylate linkers. Zhang, Jian; Nabavi, Seyede Rahele; Zhu, Dehua; Karbalaei Khani, SSarah; Zhang, Xianglei; Bigdeli, Fahime; Morsali, Ali. Materials Letters. Sep2019, Vol. 251, p140-143. 4p. DOI: 10.1016/j.matlet.2019.05.054.

The Structure and Characterization of 3,4,5-Triiodo-2-Methylthiophene: An Unexpected Iodination Product of 2-Methylthiophene. Patel, Dinesh G.; Sylvester, Eric D.; LeValley, Nicholas R.; Mitchell, Travis B.; Benedict, Jason B. Journal of Chemical Crystallography. Sep2019, Vol. 49 Issue 3, p206-212. 7p. DOI: 10.1007/s10870-019-00770-z.

Synthesis, characterization, and supramolecular architectures of two distinct classes of probes for the visualization of endogenously generated hypochlorite ions in response to cellular activity. Yadav, Richa; Odera, Keiko; Rai, Abhishek; Takahashi, Ryoya; Mishra, Lallan. Journal of Photochemistry & Photobiology B: Biology. Sep2019, Vol. 198, pN.PAG-N.PAG. 1p. DOI: 10.1016/j.jphotobiol.2019.111594.

Unexpected solvent effect on the binding of positively-charged macrocycles to neutral aromatic hydrocarbons. Wang, Yu-Mei; Yao, Huan; Quan, Mao; Chai, Hongxin; Yang, Liu-Pan; Pan, Ying-Ming; Jiang, Wei. Chemical Communications. 9/18/2019, Vol. 55 Issue 73, p10924-10927. 4p. DOI: 10.1039/c9cc06154a.

Structural verification of a tetrahydrotetrazole compound. Breton, Gary W.; Hahn, Lauren A.; Martin, Kenneth L. Acta Crystallographica: Section C, Structural Chemistry. Sep2019, Vol. 75 Issue 9, p1208-1212. 5p. DOI: 10.1107/S2053229619010210.

Identification and characterization of the first fragment hits for SETDB1 Tudor domain. Mader, Pavel; Mendoza-Sanchez, Rodrigo; Iqbal, Aman; Dong, Aiping; Dobrovetsky, Elena; Corless, Victoria B.; Liew, Sean K.; Houliston, Scott R.; De Freitas, Renato Ferreira; Smil, David; Sena, Carlo C. Dela; Kennedy, Steven; Diaz, Diego B.; Wu, Hong; Dombrovski, Ludmila; Allali-Hassani, Abdellah; Min, Jinrong; Schapira, Matthieu; Vedadi, Masoud; Brown, Peter J. Bioorganic & Medicinal Chemistry. Sep2019, Vol. 27 Issue 17, p3866-3878. 13p. DOI: 10.1016/j.bmc.2019.07.020.

Structural determinants increasing flexibility confer cold adaptation in psychrophilic phosphoglycerate kinase. Mandelman, David; Ballut, Lionel; Wolff, David A.; Feller, Georges; Gerday, Charles; Haser, Richard; Aghajari, Nushin. Extremophiles. Sep2019, Vol. 23 Issue 5, p495-506. 12p. DOI: 10.1007/s00792-019-01102-x.

Identification and Characterization of Mutations in Ubiquitin Required for Non-covalent Dimer Formation. Gabrielsen, Mads; Buetow, Lori; Kowalczyk, Dominika; Zhang, Wei; Sidhu, Sachdev S.; Huang, Danny T. Structure. Sep2019, Vol. 27 Issue 9, p1452-1452. 1p. DOI: 10.1016/j.str.2019.06.008.

Synthesis, crystal structure, phonon, magnetic and electrical properties of new molybdate Na₂Mn₂(MoO₄)₃. Jendoubi, Imen; Ptak, Maciej; Pikul, Adam; Chmielowiec, Jacek; Ciupa, Aneta; Maczka, Miroslaw; Zid, Mohamed Faouzi. Journal of Solid State Chemistry. Sep2019, Vol. 277, p738-750. 13p. DOI: 10.1016/j.jssc.2019.07.028.

Inhibition of 3-phosphoglycerate dehydrogenase (PHGDH) by indole amides abrogates de novo serine synthesis in cancer cells. Mullarky, Edouard; Xu, Jiayi; Robin, Anita D.; Huggins, David J.; Jennings, Andy; Noguchi, Naoyoshi; Olland, Andrea; Lakshminarasimhan, Damodharan; Miller, Michael; Tomita, Daisuke; Michino, Mayako; Su, Taojunfeng; Zhang, Guoan; Stamford, Andrew W.; Meinke, Peter T.; Kargman, Stacia; Cantley, Lewis C. Bioorganic & Medicinal Chemistry Letters. Sep2019, Vol. 29 Issue 17, p2503-2510. 8p. DOI: 10.1016/j.bmcl.2019.07.011.

ß-sheet elasticity of peptide self-assembly mimic, PSAM, with a grafted sequence characterized by comprehensive analyses of isomorphous crystals. Fujiwara, Hideki; Hongo, Kenta; Hori, Yuki; Yoshida, Norio; Makabe, Koki. Journal of Molecular Liquids. Sep2019, Vol. 290, pN.PAG-N.PAG. 1p. DOI: 10.1016/j.molliq.2019.111161.

Systematic investigation of the antiproliferative activity of a series of ruthenium terpyridine complexes. Karges, Johannes; Blacque, Olivier; Jakubaszek, Marta; Goud, Bruno; Goldner, Philippe; Gasser, Gilles. Journal of Inorganic Biochemistry. Sep2019, Vol. 198, p110752-110752. 1p. DOI: 10.1016/j.jinorgbio.2019.110752.

Insights into the full-length SRPK2 structure and its hydrodynamic behavior. Barbosa, Éverton de Almeida Alves; Seraphim, Thiago Vargas; Gandin, César Augusto; Teixeira, Leilane Ferreira; da Silva, Ronni Anderson Gonçalves; Righetto, Germanna L.; Goncalves, Kaliandra De Almeida; Vasconcellos, Raphael de Souza; Almeida, Márcia Rogéria; Silva Júnior, Abelardo; Fietto, Juliana Lopes Rangel; Kobarg, Jörg; Gileadi, Carina; Massirer, Katlin B.; Borges, Julio César; de Oliveira Neto, Mario; Bressan, Gustavo Costa. International Journal of Biological Macromolecules. Sep2019, Vol. 137, p205-214. 10p. DOI: 10.1016/j.ijbiomac.2019.06.135.

Structural and energetic evolution of fibrinogen toward to the betablocker interactions. González-Durruthy, Michael; Scanavachi, Gustavo; Rial, Ramón; Liu, Zhen; Cordeiro, M. Natália D.S.; Itri, Rosangela; Ruso, Juan M. International Journal of Biological Macromolecules. Sep2019, Vol. 137, p405-419. 15p. DOI: 10.1016/j.ijbiomac.2019.06.229.

Measured collagen fibril response to arterial inflation using SAXS. Wells, Hannah C.; Sizeland, Katie H.; Kirby, Nigel; Hawley, Adrian; Mudie, Stephen; Cunningham, Chris W.; Haverkamp, Richard G. International Journal of Biological Macromolecules. Sep2019, Vol. 137, p1020-1029. 10p. DOI: 10.1016/j.ijbiomac.2019.07.061.

Low-resolution SAXS and structural dynamics analysis on M. tuberculosis GmhB enzyme involved in GDP-heptose biosynthetic pathway. Karan, Sumita; Pratap, Bhanu; Ashish; Saxena, Ajay K. International Journal of Biological Macromolecules. Sep2019, Vol. 136, p676-685. 10p. DOI: 10.1016/j.ijbiomac.2019.06.035.

Book Review

The Second Kind of Impossible: The Extraordinary Quest for a New Form of Matter
By Paul J. Steinhardt
ISBN 978-1-4767-2992-3

The Second Kind of Impossible starts with Paul J. Steinhardt's 2011 expedition to the Kamchatka Peninsula in Russia. Being swarmed by mosquitoes and traipsing through muck while conducting research out in the field sounds like a typical day in the life of a wildlife biologist—not a renowned Princeton physics professor such as Steinhardt. Already, by page 2, he has the reader hooked—what on Earth was he doing there, and what was he looking for?

Steinhardt then hits rewind, taking his reader back 35 years to a presentation he gave at his alma mater, Caltech. He and his colleague, Dov Levine, had theoretically invented a new type of matter. Richard Feynman, one of Steinhardt's former professors and a member of the audience, boomed that the theory was "impossible."

Here, Steinhardt takes another step back, explaining his personal history with Feynman as a professor, and his realization that "impossible," when used by Feynman, did not necessarily mean "unachievable" or "ridiculous"—sometimes it just meant "wow!" (Steinhardt 12). All this to say, Steinhardt's presentation of "quasicrystals" violated the very laws of physics Feynman taught in his famous lectures—and Feynman was duly impressed.

Before moving forward with his quest to solve the quasicrystal mystery, Steinhardt takes another slightly larger step back, to France in the late 1700s. He lays the foundation for his story, introducing his readers to René Just Haüy, a French priest whose studies of various minerals and their physical structures earned him the moniker "The Father of Modern Crystallography."

Steinhardt also includes some helpful illustrations and detailed but digestible explanations of the fundamentals and history of crystallography in these early pages. Any crystallographer could skim over these parts, but for someone less familiar with the field, Steinhardt's clear tone and helpful descriptions early on make the narrative easy to keep up with later in the book.

One of the interesting early segues in Steinhardt's book involves Dan Shechtman, who won the Noble Prize in 2011 for the experimental proof of quasicrystals. Shechtman was working in a Maryland laboratory in the early 1980s when he discovered five-fold symmetry in a synthetic aluminum alloy-around the same time that Steinhardt was working on his theoretical explanation. But the two men were unaware of each other's research at the time. Shechtman's discovery was determined "impossible" and his paper was rejected by The Journal of Applied Physics. Steinhardt laments "if there had ever been any exchange between our two teams there is a good chance we would have joined forces and presented the theory and experiment together" (Steinhardt 79). However, if that had been the case, this would be a very different story.

The rest of the book follows Steinhardt's research into naturally occurring quasicrystals, spanning more than three decades. Quasicrystals, whether natural or man-made, break those fundamental laws Steinhardt laid out so eloquently in his first 25 pages.

The Second Kind of Impossible is a must read. Even if you have no interest in quasicrystals or five-fold crystalline structures, Steinhardt's book is a delight. The 364-page book reads like a novel—and a fast-paced, well-written one at that. Steinhardt manages to maintain a quick and thrilling pace without skimping on the science behind the story.

Review by Jeanette S. Ferrara, MA