Crystallography in the news

November 2, 2015. In a discovery that holds promise for future drug development, scientists have detected for the first time how nature performs an impressive trick to produce key chemicals similar to those in drugs that fight malaria, bacterial infections and cancer. Investigators included Yan Jessie Zhang at The University of Texas at Austin, Pinghua Liu from Boston University and Lixin Zhang from the Chinese Academy of Science.

November 2, 2015. Albert Einstein College of Medicine is taking the lead role in a five-year, $4.25 million grant awarded by the National Institutes of Health (NIH) to develop tools that can image genes and the proteins for which they code. The goal is to develop new instruments to peer into living cells and tissues of animals so that cells' innermost workings can be studied in real time. Two other institutions are involved in the project: the Howard Hughes Medical Institute (HHMI) and the University of California at Berkeley.

November 2, 2015. A team of scientists, including several from the U.S. Department of Energy's Argonne National Laboratory, has determined the structures of several important tuberculosis enzymes, which could lead to new drugs for the disease.

November 4, 2015. Scientists from Griffith University's Institute for Glycomics have mapped the world's first 3-D image of a protein linked to cancer, which could help in the development of medicines for the protein. The model was mapped by Professor Mark von Itzsteins and a team of scientists.

November 4, 2015. Two A*STAR scientists have joined 21 other scientists as EMBO Young Investigators, becoming part of an international network that represents some of the best young researchers in Europe and beyond: Dr. Khor Chiea Chuen, Group Leader at the Genome Institute of Singapore (GIS), and Dr Nicolas Plachta, Senior Principal Investigator at the Institute of Molecular and Cell Biology (IMCB).

November 9, 2015. Small molecules drug design and novel inhibitors will be the focus at the 15th annual "Advances and Progress in Drug Design" conference, which will take place on 15th-16th February 2016 in London. The event will focus on enabling biophysical tools and highlight key advancements in protein-based drug discovery, with new areas of discussion including: small molecules in drug design – a look at novel inhibitors and favorable protein-fragment interactions.

November 10, 2015. A team from the York Structural Biology Laboratory (YSBL), in the Department of Chemistry at the University of York, has produced user-friendly software called "Privateer" that enables scientists to analyse and study the three-dimensional structure of carbohydrates facilitating their exploitation in academic and modern medicine.

November 12, 2015. Researchers at Case Western Reserve University and the University of Michigan have produced the first image of an important human protein as it binds with ribonucleic acid (RNA), a discovery that could offer clues to how some viruses, including HIV, control expression of their genetic material.

Product spotlight: XtaLAB mini^™
Benchtop small molecule structure determination

In many universities, the departmental X-ray diffractometer is considered off limits to students because of fear that the instrument might be damaged by inexperienced users. The XtaLAB mini provides the opportunity for students to learn single crystal analysis by actually using a diffractometer. This is not a black box instrument. Rather, the important step of mounting a crystal on the goniometer and physically centering the crystal in the position of the X-ray beam, ensures that students learn the importance of mounting techniques and crystal selection. The simple design of the XtaLAB mini minimizes the danger of students damaging the system.

For more information about the XtaLAB mini.

Crystallographic Education in the Spotlight

This month we would like to a highlight a recent article from The Journal of Chemical Education to show how one institution is incorporating crystallography into an undergraduate laboratory class.

Simon Coles, a member of the faculty of Natural and Environmental Science of the University of Southampton, and his graduate student, Lucy Mapp, have just published an article that describes an undergraduate, hands-on practical exercise that introduces students to crystallography in a real life context. The full article is open access and can be accessed here.

S. J. Coles and L. K. Mapp
Chemistry, Faculty of Natural and Environmental Science,
University of Southampton, Southampton, SO17 1BJ, U.K.
J. Chem. Educ., Article ASAP
DOI: 10.1021/acs.jchemed.5b00071
Publication Date (Web): November 5, 2015

Abstract:
An undergraduate practical exercise has been designed to provide hands-on, instrument-based experience of advanced characterization techniques. A research experience approach is taken, centered around the concept of solid-state polymorphism, which requires a detailed knowledge of molecular and crystal structure to be gained by advanced analytical techniques normally considered as the preserve of a research facility. Powder and single crystal diffraction techniques are primarily required and implemented via the unique approach of the students themselves using benchtop instruments dedicated to teaching, as opposed to more complex and difficult to access research instruments. Furthermore, the manual instructions for performing the practical are delivered via an adapted Electronic Laboratory Notebook system where, for each specific aspect of the practical, students note their intentions, actions, observations, and inferences. Assessors can access the notebooks and provide targeted online feedback for each individual section. Evaluation of the approach is based on interviews and surveys with the first cohort of 65 students that performed the practical.

Useful link: Crystalline Insights: An X-ray Lab-Based Tutorial and Structure Determination Demo by Michael J. Vela, Tae H. Cho and Bruce M. Foxman

This site contains a downloadable PowerPoint tutorial suitable for advanced high school and above. The tutorial will run on a PC or Mac with MS PowerPoint installed. The authors ask for feedback and invite users to register for updates.

Crystal structure of the RNA-dependent RNA polymerase from influenza C virus. Hengrung, Narin; El Omari, Kamel; Serna Martin, Itziar; Vreede, Frank T.; Cusack, Stephen; Rambo, Robert P.; Vonrhein, Clemens; Bricogne, Gérard; Stuart, David I.; Grimes, Jonathan M.; Fodor, Ervin. Nature. 11/5/2015, Vol. 527 Issue 7576, p114-117. 4p. DOI: 10.1038/nature15525.

On the accuracy of unit-cell parameters in protein crystallography. Dauter, Zbigniew; Wlodawer, Alexander. Acta Crystallographica: Section D. Nov2015, Vol. 71 Issue 11, p2217-2226. 10p. DOI: 10.1107/S1399004715015503.

Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography. Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam. Bioorganic & Medicinal Chemistry. Nov2015, Vol. 23 Issue 22, p7264-7273. 10p. DOI: 10.1016/j.bmc.2015.10.024.

Development of protein seed crystals reinforced with high-strength hydrogels. Sugiyama, Shigeru; Shimizu, Noriko; Kakinouchi, Keisuke; Hiraoka, Osamu; Matsumura, Hiroyoshi; Yoshikawa, Hiroshi Y.; Takahashi, Yoshinori; Maruyama, Mihoko; Yoshimura, Masashi; Adachi, Hiroaki; Takano, Kazufumi; Murakami, Satoshi; Inoue, Tsuyoshi; Murata, Michio; Mori, Yusuke. CrystEngComm. 11/14/2015, Vol. 17 Issue 42, p8064-8071. 8p. DOI: 10.1039/c5ce00844a.

Diversity in the structures and ligand-binding sites of nematode fatty acid and retinol-binding proteins revealed by Na-FAR-1 from Necator americanus. Rey-Burusco, M. Florencia; Ibáñez-Shimabukuro, Marina; Gabrielsen, Mads; Franchini, Gisela R.; Roe, Andrew J.; Griffiths, Kate; Zhan, Bin; Cooper, Alan; Kennedy, Malcolm W.; Córsico, Betina; Smith, Brian O. Biochemical Journal. 11/1/2015, Vol. 471 Issue 3, p403-414. 12p. DOI: 10.1042/BJ20150068.

MeshAndCollect: an automated multi-crystal data-collection workflow for synchrotron macromolecular crystallography beamlines. Zander, Ulrich; Bourenkov, Gleb; Popov, Alexander N.; de Sanctis, Daniele; Svensson, Olof; McCarthy, Andrew A.; Round, Ekaterina; Gordeliy, Valentin; Mueller-Dieckmann, Christoph; Leonard, Gordon A. Acta Crystallographica: Section D. Nov2015, Vol. 71 Issue 11, p2328-2343. 16p. DOI: 10.1107/S1399004715017927

Translocation-coupled DNA cleavage by the Type ISP restriction-modification enzymes. Chand, Mahesh K; Nirwan, Neha; Diffin, Fiona M; van Aelst, Kara; Kulkarni, Manasi; Pernstich, Christian; Szczelkun, Mark D; Saikrishnan, Kayarat. Nature Chemical Biology. Nov2015, Vol. 11 Issue 11, p870-877. 8p. DOI: 10.1038/nchembio.1926.

Discovery and crystallography of bicyclic arylaminoazines as potent inhibitors of HIV-1 reverse transcriptase. Lee, Won-Gil; Frey, Kathleen M.; Gallardo-Macias, Ricardo; Spasov, Krasimir A.; Chan, Albert H.; Anderson, Karen S.; Jorgensen, William L. Bioorganic & Medicinal Chemistry Letters. Nov2015, Vol. 25 Issue 21, p4824-4827. 4p. DOI: 10.1016/j.bmcl.2015.06.074.

Structural Basis of Non-Steroidal Anti-Inflammatory Drug Diclofenac Binding to Human Serum Albumin. Zhang, Yao; Lee, Philbert; Liang, Shichu; Zhou, Zuping; Wu, Xiaoyang; Yang, Feng; Liang, Hong. Chemical Biology & Drug Design. Nov2015, Vol. 86 Issue 5, p1178-1184. 7p. DOI: 10.1111/cbdd.12583.

β-Strand mimics based on tetrahydropyridazinedione (tpd) peptide stitching. Kang, Chang Won; Sarnowski, Matthew P.; Ranatunga, Sujeewa; Wojtas, Lukasz; Metcalf, Rainer S.; Guida, Wayne C.; Del Valle, Juan R. Chemical Communications. 11/21/2015, Vol. 51 Issue 90, p16259-16262. 4p. DOI: 10.1039/c5cc07189e.

Insights into Collagen Uptake by C-type Mannose Receptors from the Crystal Structure of Endo180 Domains 1–4. Paracuellos, Patricia; Briggs, David C.; Carafoli, Federico; Loncar, Tan; Hohenester, Erhard. Structure. Nov2015, Vol. 23 Issue 11, p2133-2142. 10p. DOI: 10.1016/j.str.2015.09.004.

Structural analysis of Fc/FcγR complexes: a blueprint for antibody design. Caaveiro, Jose M. M.; Kiyoshi, Masato; Tsumoto, Kouhei. Immunological Reviews. Nov2015, Vol. 268 Issue 1, p201-221. 21p. DOI: 10.1111/imr.12365.

Elucidation of the structure of retroviral proteases: a reminiscence. Jaskolski, Mariusz; Miller, Maria; Mohana Rao, J. K.; Gustchina, Alla; Wlodawer, Alexander. FEBS Journal. Nov2015, Vol. 282 Issue 21, p4059-4066. 8p. DOI: 10.1111/febs.13397.

Crystal structure of the anion exchanger domain of human erythrocyte band 3. Arakawa, Takatoshi; Kobayashi-Yurugi, Takami; Alguel, Yilmaz; Iwanari, Hiroko; Hatae, Hinako; Iwata, Momi; Abe, Yoshito; Hino, Tomoya; Ikeda-Suno, Chiyo; Kuma, Hiroyuki; Dongchon Kang; Murata, Takeshi; Hamakubo, Takao; Cameron, Alexander D.; Kobayashi, Takuya; Hamasaki, Naotaka; Iwata, So. Science. 11/6/2015, Vol. 350 Issue 6261, p680-684. 5p. DOI: 10.1126/science.aaa4335.

Structural insights into methanol-stable variants of lipase T6 from Geobacillus stearothermophilus. Dror, Adi; Kanteev, Margarita; Kagan, Irit; Gihaz, Shalev; Shahar, Anat; Fishman, Ayelet. Applied Microbiology & Biotechnology. Nov2015, Vol. 99 Issue 22, p9449-9461. 13p. DOI: 10.1007/s00253-015-6700-4.

Leptin: From structural insights to the design of antagonists. Zabeau, Lennart; Peelman, Frank; Tavernier, Jan. Life Sciences. Nov2015, Vol. 140, p49-56. 8p. DOI: 10.1016/j.lfs.2015.04.015.

Substrate-Induced Allosteric Change in the Quaternary Structure of the Spermidine N-Acetyltransferase SpeG. Filippova, Ekaterina V.; Weigand, Steven; Osipiuk, Jerzy; Kiryukhina, Olga; Joachimiak, Andrzej; Anderson, Wayne F. Journal of Molecular Biology. Nov2015, Vol. 427 Issue 22, p3538-3553. 16p. DOI: 10.1016/j.jmb.2015.09.013.

Stabilization of Hexaborate Net with Mixed Co(II) Metal and Organic Cations: Synthesis, Rationale Characterization, Comparative Study and Enhancement of the Bioactivity. Jemai, Nabil; Rzaigui, Mohamed; Akriche, Samah. Journal of Cluster Science. Nov2015, Vol. 26 Issue 6, p2051-2064. 14p. DOI: 10.1007/s10876-015-0905-7.

Book review:

The Invention of Nature: Alexander von Humboldt's New World
By Andrea Wulf, Alfred A. Knopf, New York, 2015, 496 pp., ISBN-13: 978-0-385-35067-9

Although the subtitle suggests that The Invention of Nature is only about the New World, the book covers much more: Humboldt's early life, his trip to the new world, his attempts to visit the Himalayas stymied by the East India Company, a substitute trip to Siberia, his interactions with the scientists of his day, his publications that provided tremendous information to the general public and his later life in Berlin. The epilogue discusses one of the repercussions of WWI—the purge of everything German from many places around the world. Humboldt's current obscurity arises from his Prussian heritage and use of the German language.

I vaguely remember Humboldt as an explorer of South America from my elementary school classes – everyone learned about the Humboldt Current (at least in the US in the fourth grade in 1970). I did not realize the extent of Humboldt's travels nor his contributions to our understanding of nature. As he traveled through South America he took detailed notes and made measurements with all types of instrumentation, creating a fascinating picture of the connectivity of nature. He climbed near the summit of Mt. Chimborazo in the Andes, taking measurements all along the way in clothes that were not suitable for even a low ascent. He mapped the plant life as he ascended and ultimately correlated the types of plants he saw rising up the mountainsides with the plants one sees as one heads north from the equator to the pole.

In life Humboldt influenced the likes of Simon Bolivar, Thomas Jefferson, Ralph Waldo Emerson and Henry David Thoreau. He presented results to the Royal Society and published many works for the general public, including titles like Personal Narrative and Cosmos, bestsellers of their day.

The book does not end with Humboldt's death in 1859. After his death, his work influenced the naturalists George Perkins Marsh, Ernst Haeckel and John Muir, all of whom contributed to the creation of the national parks system in the US to preserve nature.

What Humboldt can teach us, as perhaps the first great naturalist, is that everything is connected and has a place and we need nature to survive.

Here some other interesting reads for the fall:

The Bully Pulpit: Theodore Roosevelt, William Howard Taft, and the Golden Age of Journalism by Dorothy Kearns Goodwin, Simon and Schuster, New York, 2013, 928 pages, ISBN: 978-1416547860 and Wilson by A. Scott Berg, GP Putman's Sons, New York, 2014, 832 pages, ISBN 978-0425270066. The first book is a dual biography of Theodore Roosevelt and William Howard Taft, while the latter book is the biography of Woodrow Wilson. These two books provide a detailed view of the American presidency for the first twenty years of the last century.

The Three Body Problem by Cixin Liu translated by Ken Liu, Tor Books, New York, 2006, 400 pages, ISBN: 978-0765377067. This is part one of a trilogy that includes The Dark Forest and Death's End. While some of the science (it is science fiction after all) is not quite right, I really enjoyed Part I and look forward to Part II. The premise is that we make contact with a civilization a few light years away that wants to invade to earth, but the human race has 450 years to prepare.

Joseph D. Ferrara, Ph.D.
Chief Science Officer