Protein Newsletter Volume 6, No. 5, May 2014 Crystallography in the news

In this issue: May 3, 2014. A research team led by Professor Jennifer Potts, a British Heart Foundation Senior Research Fellow in York's Department of Biology, studied how Staphylococcus Crystallography in the news aureus attach to two proteins fibronectin and fibrinogen found in human blood. News: IUCr 23rd Congress May 4, 2014. Arizona State University scientists, together with collaborators from the video of the month Chinese Academy of Sciences in Shanghai, have published a first of its kind atomic level Upcoming events look at the telomerase that may unlock the secrets to the fountain of youth. Product spotlight: BioSAXS-2000 Crystallographers in the news May 7, 2014. Soon the Advanced Photon Source (APS) will get a boost in efficiency that likely will translate into a big boon for the discovery of new pharmaceuticals. The world's Scientist spotlight: Susan Buchanan first protein characterization research facility directly attached to a light source will open Useful links for crystallography in the near future at the APS. The Advanced Protein Characterization Facility (APCF) will Survey of the month use state-of-the-art robotics for gene cloning, protein expression, protein purification and protein crystallization. Recent crystallographic papers

Book reviews May 12, 2014. Google honors Dorothy Hodgkin's X-ray vision with a molecular doodle. The event marks the 104th anniversary of the British chemist, who pioneered the use of X- rays to determine the structure of biological molecules. Special News Item IUCr 23rd Congress May 13, 2014. A key step in the decades-long mystery of the HIV life cycle was uncovered using what formerly was thought of as only a supplementary X-ray technique for structural biology. This advances study of HIV as well as highlights a powerful tool, Small Angle X-ray Scattering (SAXS), to obtain currently unobtainable high-resolution structural determination and characterization of RNA molecules.

May 14, 2014. University of Missouri researchers have completed a 3-D map of an enzyme called Proline utilization A (PutA). PutA facilitates metabolism by adding oxygen to molecules. Prof. John Tanner says mapping this enzyme will give researchers a better understanding of its function, which could help drug manufacturers create more effective drugs.

May 14, 2014. Scientists at La Trobe University published a study this week about a The Twenty-Third Congress and General Assembly of protein found in the flowers of ornamental tobacco plant that targets human cancer cells the International Union of Crystallography (IUCr 2014) and destroys them. This raises the prospect of the deepest kind of irony: tobacco grown will take place at the Palais des congrès de Montréal to produce drugs used to treat cancers caused by tobacco. from August 5-12, 2014. Located in the heart of Montréal, the Palais des congrès has gained an May 16, 2014. A new study reveals that a protein of the Ebola virus can transform into excellent reputation for its hospitality, superior services three distinct shapes, each with a separate function that is critical to the virus's survival. and functional flexible facilities. Each shape offers a potential target for developing drugs against it.

May 22, 2014. A promising anticancer agent about to enter human clinical trials is on the Science Video hook because of a chemical structure error discovered by scientists at Scripps Research Scotch tape unleashes X-ray power by unrolling it in a vacuum Institute California. The patented compound, known as TIC10 or ONC201, is owned by the biotech firm Oncoceutics. However, Scripps has applied for a patent on the corrected structure and has licensed it exclusively to another company, Sorrento Therapeutics.

May 24, 2014. MiTeGen LLC, a provider of innovative consumables for X-ray diffraction, crystallography and protein crystallization to academic, pharmaceutical, industrial and government researchers around the world, has been awarded a Phase II SBIR (Small Business Innovation Research program) award from the NIH (National Institute of Health) for the development of a rapid crystal cooling device ("hyperquencher") for cryocrystallography and other sciences requiring safe, controlled, high-speed cooling of samples.

New product introduction: Rigaku BioSAXS-2000 Researchers at the University of California, Los Angeles, have shown that it is possible to produce X- Rigaku's new BioSAXS-2000 SAXS camera is designed specifically to rays by simply unrolling Scotch tape. In the journal , Dr. Putterman and his colleagues report that meet the needs of the structural biologist and, with improved flux, surprisingly fierce flows of electrons were unleashed as now increases throughput for home lab experiments. the tape was unpeeled and its gooey adhesive snapped free of the surface. The electrical currents, in The BioSAXS-2000 is equipped with the new OptiSAXS optic, a turn, generated strong, short bursts of X-rays — each doubly focusing multilayer optic whose focus is at the detector. The OptiSAXS provides burst, about a billionth of a second long, contained better than two fold improvement in flux compared to it's predecessor resulting in higher about 300,000 X-ray photons. brilliance at the sample position and data collection times in the range of minutes. Thus, the BioSAXS-2000 brings a beamline experience to home laboratory SAXS experiments.

Optional accessories include an Automatic Sample Changer (ASC) with support for 8 or 96 samples and the Automatic Analysis Pipeline (AAP) based on ATSAS, the world's most popular SAXS analysis software developed at EMBL Hamburg.

Ask for more information.

Lab spotlight: Susan Buchanan @ NIH

Susan Buchanan, Ph.D. Principal Investigator, NIDDK Bethesda, MD 20892

Dr. Buchanan is Chief of the Section on Structural Biology of Membrane Proteins in the National Institute for Diabetes & Digestive & Kidney Diseases, at the National Institutes of Health. She received her Ph.D. from the Johann-Wolfgang-Goethe Universität in Frankfurt, Germany in 1990. She completed postdoctoral fellowships at the MRC Laboratory of , Cambridge, UK, and at UT Southwestern Medical Center, Dallas, before returning to the UK to establish a research group at Birkbeck College, London in 1998. She joined the NIDDK as a tenure track investigator in 2001 and is currently a senior investigator in the Laboratory of Molecular Biology, NIDDK.

The focus of her group's research program is the structure determination of integral membrane proteins by X-ray crystallography and functional analysis of these proteins using biophysical, biochemical, and cell biological techniques. They study transporters embedded in the outer membranes of Gram-negative bacteria, which are surface accessible and therefore have the potential to be good vaccine and/or chemotherapeutic New Rigaku BioSAXS-2000 targets against infectious diseases. They also study the membrane associated or soluble protein partners that interact with outer membrane transporters to better understand how these systems function in vivo. Current topics in the lab include [1] small molecule and protein import across the bacterial outer membrane, [2] protein secretion by pathogenic Crystallographers in the News bacteria, and [3] protein import across mitochondrial outer membranes. Crystallographers Elected Fellows of the Royal Society 2014

Professor FRS, Principal Research Fellow, Professor of Protein Crystallography, Cambridge Institute for Medical Research, University of Cambridge.

Professor Read is known internationally for his outstanding and fundamental contributions to the development of macromolecular crystallographic software. His application of maximum likelihood based algorithms to the solution of macromolecular crystal structures by molecular replacement (a technique that uses the known structure of a homologue to solve an unknown structure) has resulted in software (Phaser) that is foremost in the field. He also devised and demonstra - Useful link: DNAWorks (v3.2.2) ted an improved likelihood target function for model refinement that has been adopted by all major refinement programs. In addition, Professor Read has DNAWorks (v3.2.2) - Automatic oligonucleotide design for PCR-based gene synthesis. The led structural work that has made significant contribu - availability of sequences of entire genomes has dramatically increased the number of tions to understanding the mechanisms of proteins protein targets, many of which will need to be overexpressed in cells other than the relevant to disease (bacterial toxins and ). original source of DNA. Gene synthesis often provides a fast and economically efficient approach. The synthetic gene can be optimized for expression and constructed for easy mutational manipulation without regard to the parent genome. Yet design and construction of synthetic genes, especially those coding for large proteins, can be a slow, Professor FMedSci FRS, Professor of Chemical Biology difficult and confusing process. DNAWorks automates the design of oligonucleotides for and Director of Biomedical Sciences gene synthesis by PCR-based methods. Research Complex, . A description of DNAWorks can be found: (Hoover, D. and Lubkowski, J., 2002).

Professor Naismith is cited for his stunning structural and chemical dissection of the many proteins involved in recognition, synthesis and Selected recent crystallographic papers export. His work has revealed new paradigms in the recognition of nucleic acids and , Applications of direct methods in protein crystallography for dealing with unveiled novel chemical mechanisms for enzymatic diffraction data down to 5Å resolution. Fan, Haifu; Gu, Yuanxin; He, Yao; Lin, nucleophilic substitution and addition and provided the Zhengjiong; Wang, Jiawei; Yao, Deqiang; Zhang, Tao. Acta Crystallographica. Section A, first views, both structural and dynamic, of Foundations & Advances. polysaccharide export systems in bacteria. His work is May2014, Vol. 70 Issue 3, p239-247. 9p. characterised by a synthesis of three-dimensional http://dx.doi.org/10.1107/S2053273313034864. structural under standing with profound chemical insight. Molecular dynamics simulation of protein effects on interfacial energy between HA surfaces and solutions. Wang, Kefeng; Leng, Yang; Lu, Xiong; Ren, Fuzeng. Materials Letters. May2014, Vol. 123, p191-194. 4p. http://dx.doi.org/10.1016/j.matlet.2014.02.089. Upcoming Events

Structural insights into bacterial resistance to cerulenin. Trajtenberg, Felipe; Protein Structure, Function and Malfunction (PSFaM) Altabe, Silvia; Larrieux, Nicole; Ficarra, Florencia; Mendoza, Diego; Buschiazzo, Alejandro; Meeting is Jun 14 2014 to Jun 15 2014 in Saskatoon, FEBS Journal SK, Canada. Schujman, Gustavo E. . May2014, Vol. 281 Issue 10, p2324-2338. 15p. http://dx.doi.org/10.1111/febs.12785. Northwest Crystallography Workshop is Jun 20 2014 to Jun 22 2014 in Corvallis, OR. Channelrhodopsin unchained: Structure and mechanism of a light-gated cation channel. Lórenz-Fonfría, Víctor A.; Heberle, Joachim. BBA - Bioenergetics. May2014, Vol. Machines on Genes: Nucleir Acid (FASEB) is 1837 Issue 5, p626-642. 17p. http://dx.doi.org/10.1016/j.bbabio.2013.10.014. Jun 22 2014 to Jun 27 2014 in Snow Mass, CO.

Asymmetric perturbations of signalling oligomers. Maksay, Gábor; Toke, Orsolya. ACA Summer Course for Chemical Crystallography is Progress in Biophysics & Molecular Biology Jul 7 2014 to Jul 17 2014 in Notre Dame, IN. . May2014, Vol. 114 Issue 3, p153-169. 17p. http://dx.doi.org/10.1016/j.pbiomolbio.2014.03.001. The 28th Protein Society Symposium will be held July 27-30, 2014 in San Diego, CA. Comparison of Binding Characterization of Two Antiviral Drugs to Human Serum Albumin. Li, Mei; McAuley, Erin; Zhang, Yao; Kong, LinLin; Yang, Feng; Zhou, Diffraction Methods in Structural Biology is Aug 4 2014 ZuPing; Wu, XiaoYang; Liang, Hong. Chemical Biology & Drug Design. May2014, Vol. 83 to Aug 9 2014 in Lewiston, ME. Issue 5, p576-582. 7p. http://dx.doi.org/10.1111/cbdd.12270.

Twenty-Third Congress and General Assembly of the International Union of Crystallography (IUCr 2014) will 2dx_automator: Implementation of a semiautomatic high-throughput high- be held Aug 5-12, 2014 in Montreal, Canada. resolution cryo-electron crystallography pipeline. Scherer, Sebastian; Kowal, Julia; Chami, Mohamed; Dandey, Venkata; Arheit, Marcel; Ringler, Philippe; Stahlberg, Henning. Journal of Structural Biology . May2014, Vol. 186 Issue 2, p302-307. 6p. http://dx.doi.org/10.1016/j.jsb.2014.03.016.

Structure determination of α-helical membrane proteins by solution-state Survey of the Month NMR: Emphasis on retinal proteins. Gautier, Antoine. BBA - Bioenergetics. May2014, Vol. 1837 Issue 5, p578-588. 11p. http://dx.doi.org/10.1016/j.bbabio.2013.06.009.

Relevance of rhodopsin studies for GPCR activation. Deupi, Xavier. BBA - Bioenergetics. May2014, Vol. 1837 Issue 5, p674-682. 9p. http://dx.doi.org/10.1016/j.bbabio.2013.09.002.

Diphtheria toxin conformational switching at acidic pH. Leka, Oneda; Vallese, Francesca; Pirazzini, Marco; Berto, Paola; Montecucco, Cesare; Zanotti, Giuseppe. FEBS Journal. May2014, Vol. 281 Issue 9, p2115-2122. 8p. http://dx.doi.org/10.1111/febs.12783.

High Resolution Structure and Double Electron-Electron Resonance of the Zebrafish Voltage-dependent Anion Channel 2 Reveal an Oligomeric Population. Schredelseker, Johann; Paz, Aviv; López, Carlos J.; Altenbach, Christian; Leung, Calvin S.; Drexler, Maria K.; Jau-Nian Chen; Hubbell, Wayne L.; Abramson, Jeff. Journal of Biological . 5/2/2014, Vol. 289 Issue 18, p12566-12577. 12p. http://dx.doi.org/10.1074/jbc.M113.497438.

Picolinic acid based Cu(II) complexes with heterocyclic bases - Crystal structure, DNA binding and cleavage studies. Pulimamidi, Rabindra Reddy; Nomula, Raju; Pallepogu, Raghavaiah; Shaik, Hussain. European Journal of Medicinal Chemistry. May2014, Vol. 79, p117-127. 11p. http://dx.doi.org/10.1016/j.ejmech.2014.03.084.

Water channel structures analysed by electron crystallography. Tani, Kazutoshi; Fujiyoshi, Yoshinori. BBA - General Subjects. May2014, Vol. 1840 Issue 5, p1605-1613. 9p. http://dx.doi.org/10.1016/j.bbagen.2013.10.007.

Last Month's Survey L-Asp is a useful tool in the purification of the ionotropic glutamate receptor A2 ligand-binding domain. Krintel, Christian; Frydenvang, Karla; Ceravalls de Rabassa, FEBS Japan has Mt. Fuji, Paris has the Eiffel Tower, and Anna; Kærn, Anne M.; Gajhede, Michael; Pickering, Darryl S.; Kastrup, Jette S. London has Big Ben. What is the single most iconic Journal. May2014, Vol. 281 Issue 10, p2422-2430. 9p. image that represents structural biology? http://dx.doi.org/10.1111/febs.12795.

A New Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8 Bound to DNA Gyrase Gives Fresh Insight into the Mechanism of Inhibition. Hearnshaw, Stephen J.; Edwards, Marcus J.; Stevenson, Clare E.; Lawson, David M.; Maxwell, Anthony. Journal of Molecular Biology. May2014, Vol. 426 Issue 10, p2023-2033. 11p. http://dx.doi.org/10.1016/j.jmb.2014.02.017.

The structure of AAVrh32.33, a novel gene delivery vector. Mikals, Kyle; Nam, Hyun-Joo; Van Vliet, Kim; Vandenberghe, Luk H.; Mays, Lauren E.; McKenna, Robert; Wilson, James M.; Agbandje-McKenna, Mavis. Journal of Structural Biology. May2014, Vol. 186 Issue 2, p308-317. 10p. http://dx.doi.org/10.1016/j.jsb.2014.03.020.

Crystal structure of a mutant of archaeal ribosomal protein L1 from Methanococcus jannaschii. Sarskikh, A.; Gabdulkhakov, A.; Kostareva, O.; Shklyaeva, A.; Tishchenko, S. Crystallography Reports. May2014, Vol. 59 Issue 3, p394-398. 5p. http://dx.doi.org/10.1134/S1063774514030158.

Cysteine co-oxidation process driven by native peptide folding: an example on HER2 receptor model system. Calce, Enrica; Sandomenico, Annamaria; Saviano, Michele; Ruvo, Menotti; De Luca, Stefania. Amino Acids. May2014, Vol. 46 Issue 5, p1197-1206. 10p. http://dx.doi.org/10.1007/s00726-014-1681-7.

Synthesis, growth, characterization, structure and molecular docking studies of 1-[(E)-{[4-(morpholin-4-yl)phenyl]imino} methyl]naphthalen-2-ol single crystal: A potential antimicrobial agent. Ranjith, S.; Sugumar, P.; Rajagopal, G.; Udayakumar, M.; Ponnuswamy, M.N. Journal of Molecular Structure. May2014, Vol. 1065- 1066, p21-28. 8p. http://dx.doi.org/10.1016/j.molstruc.2014.02.025.

Structural and Molecular Basis of the Peroxynitrite-mediated Nitration and Inactivation of Trypanosoma cruzi Iron-Superoxide Dismutases (Fe-SODs) A and B. Martinez, Alejandra; Peluffo, Gonzalo; Petruk, Ariel A.; Hugo, Martín; Piñeyro, Dolores; Demicheli, Verónica; Moreno, Diego M.; Lima, Analía; Batthyány, Carlos; Durán, Rosario; Robello, Carlos; Martí, Marcelo A.; Larrieux, Nicole; Buschiazzo, Alejandro; Trujillo, Madia; Radi, Rafael; Piacenza, Lucía. Journal of Biological Chemistry. 5/2/2014, Vol. 289 Issue 18, p12760-12778. 19p. http://dx.doi.org/10.1074/jbc.M113.545590.

Book review: Celestial Sleuth: Using Astronomy to Solve Mysteries in Art, History, and Literature by Donald W. Olson Springer Praxis Books, New York, 2014, 355 pages. ISBN 978-1-4614-8403-5.

It may not seem like the unsolved mysteries of art, history, and literature could have anything to do with astronomy, but physicist Donald W. Olson seeks to prove otherwise in his new book, Celestial Sleuth. As the title suggests, Olson implements the tools of astronomy to solve a select number of mysteries in these fields. The book should be just as enjoyable for a lover of art as a fan of physics. Despite the somewhat complicated astronomical theories applied to solve these "mysteries," Olson does a decent job of explaining these concepts so that the average layman can understand exactly how he solves them.

First, Olson seeks to answer a number of questions about the time and location, as well as the celestial accuracy of a number of famous paintings, including those by Monet, van Gogh, and Munch. Olson and his team used celestial markers in the paintings to determine the exact time and location of the scenes depicted in the paintings.

Then, Olson approaches a series of historical questions. I found his interest in debunking the urban legend that the Boston Tea Party occurred under a full moon quite intriguing. As Olson and his team eventually proved, the Boston Tea Party really occurred under the cover of almost total darkness, as the moon would have been a thin waxing crescent on that night.

Finally, Olson wraps up the book with an astronomically driven approach to literature, which he breaks into two categories, pre-1800 and post-1800. Of these discussions, I was most intrigued by Olson's interest in Shakespeare's Hamlet and its description of a "bright star" burning in the first act. He ultimately reaches the conclusion that Shakespeare was actually describing a famous supernova that happened in 1572. As a budding Shakespearean scholar, I found it interesting that such a brief yet iconic moment in one of his works could in fact be rooted in a real-life astronomical event.

I found it particularly helpful that the book has numerous illustrations, including reproductions of the paintings Olson discusses, relevant photographs of the night sky and landscape, as well as a few documentary photographs of Olson and his team from Texas State University.

I wasn't sure what to expect when I began reading this book, and although at times it seemed to me like Olson used astronomy as an umbrella concept under which to draw conclusions about art, history and literature, it was a good and relatively quick read.

Jeanette S. Ferrara, Princeton, Class of 2015

Flash Boys: A Wall Street Revolt by Michal Lewis, W. W. Norton and Co., New York, 2014, 288 pages, ISBN: 978-0-393-24463-3.

This is a very detailed and extremely interesting analysis of high frequency trading or, as it is more rightly called, time delay trading. This book will make you wonder if your IRA or 401(k) is a safe investment since predators are skimming off the top on every trade. I am glad that the U.S. did not convert Social Security to the stock market.

Capital in the 21st Century by Thomas Piketty, Translated by Arthur Goldkamp, President and Fellows of the College of Harvard, 2014, 696 pages, ISBN 978-0674430006.

This book has been on the Amazon #1 list for a while and has been the talk of the left, right, center and the 1%. Any book that starts off with "Indeed, the distribution of wealth is too important an issue to be left to economists, sociologists, historians and philosophers" is going be good. At this point I am only about 25% through, but I would put this book on a par with Adam Smith's The Wealth of Nations. Just after I submitted this mini-review Science magazine (May 23, 2014) published a special section on the Science of Inequality, which includes an analysis of the book as well a review article by the author.

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

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