Crystallography in the News
August 1, 2019. An experimental vaccine against respiratory syncytial virus (RSV), one of the leading causes of infectious disease deaths in infants, has shown early promise in a Phase 1 human clinical trial. Using protein crystallography, a team of researchers (including The University of Texas at Austin’s Jason McLellan) reported that one dose of their vaccine candidate elicited large increases in RSV-neutralizing antibodies that were sustained for several months.
August 1, 2019. Researchers have identified key sections of a bacterial enzyme MraY that could be targeted with new drugs to inhibit the spread of some bacterial infections. A team of scientists from Hokkaido University in Japan, Duke University in the U.S. and The Catholic University of Korea recently published their findings. Five types of natural products have been discovered to have inhibitory activities against MraY.
August 8, 2019. Mark Schlossman, professor of physics at the University of Illinois at Chicago, has received a $14.1 million, five-year grant from the National Science Foundation to expand the experimental capabilities at NSF's Chemistry and Materials Center for Advanced Radiation Sources, also known as NSF's ChemMatCARS.
August 14, 2019. Certain types of toxic algae secrete saxitoxin, one of the world’s most lethal
neurotoxins, but freshwater frogs are unaffected as they make proteins that sequester saxitoxin. Recently, a team led by Daniel Minor, at UCSF, used X-ray crystallography to solve the structure of saxiphilin, an antitoxin protein collected from American bullfrogs. They determined how saxiphilin binds with saxitoxin to render it harmless.
August 15, 2019. The National Institutes of Health (NIH) awarded Cornell $17.4 million for MacCHESS (Macromolecular X-ray science at the Cornell High Energy Synchrotron Source), a subfacility of CHESS that attracts hundreds of biomedical researchers each year. As part of its Empire State Development Division of Science, Technology and Innovation (NYSTAR) program to promote jobs in the state, New York state will augment the award with up to $2.5 million over the next five years.
August 15, 2019. Using X-ray crystallography, researchers in Japan and the U.K. have uncovered an unusual protein activity in rice that can be exploited to give crops an edge in the evolutionary arms race against rice blast disease, a major threat to rice production around the world. Magnaporthe oryzae, the fungus that leads to rice blast disease, creates lesions on rice plants that reduce the yield and quality of grain.
August 16, 2019. Mario Wriedt, Associate Professor of Chemistry & Biomolecular Science and CAMP Distinguished Professor at Clarkson University, recently offered an intensive 4-day Single Crystal X-ray Diffraction (SCXRD) workshop, Problems, Errors & Pitfalls in Single Crystal Structure Analysis, at Clarkson University’s Main Campus, Potsdam NY, in early August. Rigaku is proud to have been a cosponsor of this workshop.
Product Spotlight
HyPix-Arc 150°: Curved photon counting X-ray detector
Rigaku
HyPix-Arc 150° is a unique, curved Hybrid Photon Counting (HPC) X-ray detector for single crystal diffraction applications. HyPix-Arc 150° has the highest 2θ range at a single position available for the home lab.
Collect more data in a single exposure with less reflection profile distortion.
The HyPix-Arc 150° offers 150 degrees angular coverage from edge to edge. This is more than enough to collect complete single crystal diffraction data, according to IUCr guidelines, for even Cu Kα X-ray wavelength from a single theta position. High and low angle data are measured at the same time, under the same conditions for better scaling, faster data and reduced dose time. A curved detector minimizes peak distortion by ensuring that, even at short crystal-to-detector distances, diffracted beams are closer to perpendicular than is possible with a flat geometry.
Features:
- Lowest reflection profile distortion
- Faster data collection
- Higher 2θ coverage in a single image
- All reflections measured under the same conditions
- Capture more diffracted photons per exposure
Lab in the Spotlight
Department of Chemistry at Emory University
In June of 2017, the first XtaLAB Synergy-S in the Western Hemisphere was
installed at the Department of Chemistry at Emory University. In just over two years the instrument, at the guidance of John Bacsa, has produced over 1000 structures. The
XtaLAB Synergy-S was purchased through an award from the National Science Federation. The
XtaLAB Synergy-S includes copper and molybdenum PhotonJet sources equipped with Osmic optics, and the proven Rigaku HyPix-6000HE Hybrid Photon Counting (HPC) detector. The advanced high-brilliance sources and a HPC detector with its small pixel size and zero background noise assist in collecting data from the very small crystals, poorly crystalline materials, biological materials and even protein crystals that make up the more than one thousand successful structures.
Dr. John Bacsa
Facilities Director
Crystallography Lab, Emory University
email: jbacsa[at]emory.edu
Synergy-S at Emory has produced over 1000 structures! John is on the far right.
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Selected Recent Crystallographic Papers
New discovery in crystallography: correlation of terahertz time-domain spectra with crystal structures and photoluminescence properties of mononuclear/binuclear diimine–Cu(i)-phosphine complexes. Zhu, Ning; Wang, Guo; Lin, Sen; Li, Zhong-Feng; Xin, Xiu-Lan; Yang, Yu-Ping; Liu, Min; Jin, Qiong-Hua. CrystEngComm. 8/7/2019, Vol. 21 Issue 29, p4275-4288. 14p. DOI: 10.1039/c9ce00729f.
BraggNet: integrating Bragg peaks using neural networks. Sullivan, Brendan; Archibald, Rick; Azadmanesh, Jahaun; Vandavasi, Venu Gopal; Langan, Patricia S.; Coates, Leighton; Lynch, Vickie; Langan, Paul. Journal of Applied Crystallography. Aug2019, Vol. 52 Issue 4, p854-863. 10p. DOI: 10.1107/S1600576719008665.
A nanoporous metal–organic framework as a renewable size-selective hydrogen-bonding catalyst in water. Liu, Yanhong; Ma, Ju; Wu, Pengyan; Zheng, Jia-Jia; Tian, Xueqin; Jiang, Min; He, Yumei; Dong, Han; Wang, Jian. Dalton Transactions: An International Journal of Inorganic Chemistry. 8/21/2019, Vol. 48 Issue 31, p11855-11861. 7p. DOI: 10.1039/c9dt01763a.
Synthesis and structure of magnesium aminopyridinates and their attempted conversion to magnesium (I) derivatives. Noor, Awal; Qayyum, Sadaf; Fertig, Robin. Inorganica Chimica Acta. Aug2019, Vol. 494, p239-244. 6p. DOI: 10.1016/j.ica.2019.05.025.
Crystal structure, Hirshfeld analysis and HSA interaction studies of N'-[(E)-(5-bromothiophen-2-yl)methylidene]-3-hydroxynaphthalene-2-carbohydrazide. Kumar, Savithri; Vasantha Kumar, Basappa Chidananda; Chandra; Revanasiddappa, Hosakere Doddarevanna. Journal of Molecular Structure. Aug2019, Vol. 1189, p343-351. 9p. DOI: 10.1016/j.molstruc.2019.03.070.
Three thymine/adenine binding modes of the ruthenium complex Λ-[Ru(TAP)2(dppz)]2+ to the G-quadruplex forming sequence d(TAGGGTT) shown by X-ray crystallography. McQuaid, Kane; Hall, James P.; Baumgaertner, Lena; Cardin, David J.; Cardin, Christine J. Chemical Communications. 8/11/2019, Vol. 55 Issue 62, p9116-9119. 4p. DOI: 10.1039/c9cc04316k.
A novel structurally characterized haloacid dehalogenase superfamily phosphatase from Thermococcus thioreducens with diverse substrate specificity. Havlickova, Petra; Brinsa, Vitezslav; Brynda, Jiri; Pachl, Petr; Prudnikova, Tatyana; Mesters, Jeroen R.; Kascakova, Barbora; Kuty, Michal; Pusey, Marc L.; Ng, Joseph D.; Rezacova, Pavlina; Kuta Smatanova, Ivana. Acta Crystallographica: Section D, Structural Biology. Aug2019, Vol. 75 Issue 8, p743-752. 10p. DOI: 10.1107/S2059798319009586.
X-ray crystallographic structure and oligomerization of Gloeobacter rhodopsin. Morizumi, Takefumi; Ou, Wei-Lin; Van Eps, Ned; Inoue, Keiichi; Kandori, Hideki; Brown, Leonid S.; Ernst, Oliver P. Scientific Reports. 8/2/2019, Vol. 9 Issue 1, pN.PAG-N.PAG. 1p. DOI: 10.1038/s41598-019-47445-5.
A Ubiquitin-Binding Domain that Binds a Structural Fold Distinct from that of Ubiquitin. Lim, Michael; Newman, Joseph A.; Williams, Hannah L.; Masino, Laura; Aitkenhead, Hazel; Gravard, Angeline E.; Gileadi, Opher; Svejstrup, Jesper Q. Structure. Aug2019, Vol. 27 Issue 8, p1316-1316. 1p. DOI: 10.1016/j.str.2019.05.003.
NHC copper complexes functionalized with sulfoxide and sulfone moieties. Szadkowska, Anna; Pawlowski, Robert; Zaorska, Ewelina; Staszko, Sebastian; Trzybinski, Damian; Wozniak, Krzysztof. Applied Organometallic Chemistry. Aug2019, Vol. 33 Issue 8, pN.PAG-N.PAG. 1p. DOI: 10.1002/aoc.4983.
Highly oxygenated meroterpenoids from the Antarctic fungus Aspergillus terreus. Feng, Wenya; Chen, Chunmei; Mo, Shuyuan; Qi, Changxing; Gong, Jiaojiao; Li, Xiao-Nian; Zhou, Qun; Zhou, Yuan; Li, Dongyan; Lai, Yongji; Zhu, Hucheng; Wang, Jianping; Zhang, Yonghui. Phytochemistry. Aug2019, Vol. 164, p184-191. 8p. DOI: 10.1016/j.phytochem.2019.05.015.
Crystal structure of the 65-kilodalton amino-terminal fragment of DNA topoisomerase I from the gram-positive model organism Streptococcus mutans. Jones, Jesse A.; Hevener, Kirk E. Biochemical & Biophysical Research Communications. Aug2019, Vol. 516 Issue 2, p333-338. 6p. DOI: 10.1016/j.bbrc.2019.06.034.
Rare-earth complexes of the asymmetric amide ligands, N(SiMe3)Ph and N(SiMe3)Cy. Moehring, Samuel A.; Ziller, Joseph W.; Evans, William J. Polyhedron. Aug2019, Vol. 168, p72-79. 8p. DOI: 10.1016/j.poly.2019.04.026.
Sonochemical synthesis, structural characterizations and antibacterial activities of biocompatible Copper(II) coordination polymer nanostructures. Usefi, Sahar; Akhbari, Kamran; White, Jonathan. Journal of Solid State Chemistry. Aug2019, Vol. 276, p61-67. 7p. DOI: 10.1016/j.jssc.2019.04.016.
Strophasterols E and F: Rearranged ergostane-type sterols from Pleurotus eryngii. Kikuchi, Takashi; Isobe, Maya; Uno, Sawako; In, Yasuko; Zhang, Jie; Yamada, Takeshi. Bioorganic Chemistry. Aug2019, Vol. 89, p103011-103011. 1p. DOI: 10.1016/j.bioorg.2019.103011.
A new crystal form of human acetylcholinesterase for exploratory room-temperature crystallography studies. Gerlits, Oksana; Ho, Kwok-Yiu; Cheng, Xiaolin; Blumenthal, Donald; Taylor, Palmer; Kovalevsky, Andrey; Radic, Zoran. Chemico-Biological Interactions. Aug2019, Vol. 309, p108698-108698. 1p. DOI: 10.1016/j.cbi.2019.06.011.
An update about the crucial role of stereochemistry on the effects of Peroxisome Proliferator-Activated Receptor ligands. Laghezza, Antonio; Piemontese, Luca; Tortorella, Paolo; Loiodice, Fulvio. European Journal of Medicinal Chemistry. Aug2019, Vol. 176, p326-342. 17p. DOI: 10.1016/j.ejmech.2019.05.012.
Aggregation-induced emission enhancement and reversible mechanochromic luminescence of quinoline-based zinc(ii)–Schiff base complexes. Qiao, Di; Wang, Jin-Yun; Zhang, Li-Yi; Dai, Feng-Rong; Chen, Zhong-Ning. Dalton Transactions: An International Journal of Inorganic Chemistry. 8/7/2019, Vol. 48 Issue 29, p11045-11051. 7p. DOI: 10.1039/c9dt02177a.
Macozinone: revised synthesis and crystal structure of a promising new drug for treating drug-sensitive and drug-resistant tuberculosis. Zhang, Gang; Aldrich, Courtney C. Acta Crystallographica: Section C, Structural Chemistry. Aug2019, Vol. 75 Issue 8, p1031-1035. 5p. DOI: 10.1107/S2053229619009185.
Reactivity and Catalytic Activity of Homobimetallic Vanadium(V) Complex Derived from Bis(5-chlorosalicylaldehyde)oxaloyldihydrazone Ligand. Syiemlieh, Ibanphylla; Asthana, Mrityunjaya; Lal, Ram A. Applied Organometallic Chemistry. Aug2019, Vol. 33 Issue 8, pN.PAG-N.PAG. 1p. DOI: 10.1002/aoc.4984.
Enhancing Stability and Reducing Viscosity of a Monoclonal Antibody With Cosolutes by Weakening Protein-Protein Interactions. Dear, Barton J.; Hung, Jessica J.; Laber, Joshua R.; Wilks, Logan R.; Sharma, Ayush; Truskett, Thomas M.; Johnston, Keith P. Journal of Pharmaceutical Sciences. Aug2019, Vol. 108 Issue 8, p2517-2526. 10p. DOI: 110.1016/j.xphs.2019.03.008.
Dynamic Properties of Human α-Synuclein Related to Propensity to Amyloid Fibril Formation. Fujiwara, Satoru; Kono, Fumiaki; Matsuo, Tatsuhito; Sugimoto, Yasunobu; Matsumoto, Tomoharu; Narita, Akihiro; Shibata, Kaoru. Journal of Molecular Biology. Aug2019, Vol. 431 Issue 17, p3229-3245. 17p. DOI: 10.1016/j.jmb.2019.05.047.
Structure of the Human TRPML2 Ion Channel Extracytosolic/Lumenal Domain. Viet, Kerstin K.; Wagner, Annika; Schwickert, Kevin; Hellwig, Nils; Brennich, Martha; Bader, Nicole; Schirmeister, Tanja; Morgner, Nina; Schindelin, Hermann; Hellmich, Ute A. Structure. Aug2019, Vol. 27 Issue 8, p1246-1246. 1p. DOI: 10.1016/j.str.2019.04.016.
Functional Relevance of Interleukin-1 Receptor Inter-domain Flexibility for Cytokine Binding and Signaling. Ge, Jiwan; Remesh, Soumya G.; Hammel, Michal; Pan, Si; Mahan, Andrew D.; Wang, Shuying; Wang, Xinquan. Structure. Aug2019, Vol. 27 Issue 8, p1296-1296. 1p. DOI: 10.1016/j.str.2019.05.011.
Book Review
Bottle of Lies: The Inside Story of the Generic Drug Boom
By Katherine Eban
ISBN 978-0-06-233878-5
Katherine Eban's Bottle of Lies is a remarkable piece of
investigative journalism, one she has been working on for over a
decade, though the story she tells has roots digging even decades
deeper. The focus of her narrative is the Indian pharmaceutical company
Ranbaxy Laboratories. Founded by the Singhs in 1961, Ranbaxy was
operated by the family for the majority of its years of operation.
Despite being worth billions of dollars, the Singhs ran Ranbaxy like
the family-owned-and-operated corporation it was. The company
essentially folded in 2014 when it was absorbed by Sun Pharma in the
wake of enormous controversy, including recalls and reports of glass
fragments in prescription capsules.
But, as Eban herself admits in her opening Author's Note, her interest in generic prescription drugs did not start with Ranbaxy. In 2008, the host of an NPR radio show called The People's Pharmacy reached out to Eban with concerns expressed by his listeners that their generic drug replacements for brand-name pharmaceuticals were not working. Patients with an established brand-name drug regimen found themselves relapsing when their prescriptions switched to the cheaper, more affordable generic version. Eban did what investigative reporters do best--she investigated. Her first piece on generic drugs was published in Self in 2009. It was her reporting for that first article that inspired Bottle of Lies.
Ranbaxy was the focus of an investigative follow-up piece Eban wrote for Fortune in 2013. It was in May of that year that the corporation's corrupt manufacturing and management practices became the center of media attention. Felony charges were brought against the company in the United States as the result of more than half a decade of FDA investigations, sparked by the actions of a single whistleblower: Dinesh Thakur. The company pleaded guilty, to the tune of a $500 million dollar settlement.
Ranbaxy's fall from grace--it went from winning awards for brand trust to publicly pleading guilty to multiple felony drug fraud counts--consumes the majority of Eban's narrative. Her key protagonist, Dinesh Thakur, is the former employee turned whistleblower who brought evidence of the company's malpractice to the FDA. Thakur's journey, from a respected employee at Bristol Meyers-Squibb, one of America's prestige brand-name pharmaceutical companies, to one who resigned amidst a cloud of controversy at a generic drug company in India, provides a lens through which Eban encourages her readers to view the web of lies and deceit that dominate the generic drug industry.
The Ranbaxy news is already over half a decade old at this point. There is some semblance of justice as one reads, knowing the bad guys got caught, so to speak. Reading Bottle of Lies is like watching The Untouchables--you know Elliot Ness got Al Capone in the end, because Capone died in jail. But you still watch the movie because you want to know how--and that's why you need to read Bottle of Lies.
Though Thakur dominates much of the narrative, other crusaders of pharmaceutical justice make noteworthy and repeated appearances, such as FDA inspector Peter Baker. Baker uncovered the unsettling reality that generic drug companies not only manufacture and distribute defective drugs to American consumers, they do so around the world. Often, the generics shipped to third-world countries in Africa are those that did not pass muster to be sent to the United States. We may not be getting the good stuff, but Americans are also not the ones getting the worst stuff.
At the heart of the generic drug controversy is the very definition upon which they are based: bioequivalence. As long as a generic drug has the same amount of active ingredient (give or take) as the name-brand drug for which it is being substituted, it is considered an equal substitution. But there is a lot more to prescription medication than active ingredients, and not all generics are created equal. At the end of the day, do generics cost less money to purchase at the pharmacy than name-brand prescriptions? Oftentimes, insurance covers the full cost of the generic, rendering it seemingly free to the average consumer. But the real cost of generic prescription medication is often that of patient health.
If you have ever taken a generic prescription medication, you need to read this book, especially if you take a generic prescription medication on a regular basis.
*Disclosure: Katherine Eban spoke to a class I attended as a journalism student at NYU about her reporting on Ranbaxy, and the process by which she conducted her investigative reporting.
Review by Jeanette S. Ferrara, MA
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