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Protein Crystallography NewsletterVolume 4, No. 8, August 2012

In this issue:

Crystallography news summary

Special meeting report

Lab spotlight: Prof. Jianping Ding

Useful tools for structural biology

Product spotlight: PlateMate

Science video of the month

Crystallographers in the news

Survey of the month

Monthly crystallographic papers

Book review

Special Meeting Report Chinese Crystallographic Society

The fifth general assembly and academic congress ofthe Chinese Crystallographic Society was held in Xian,China August 20-23. This meeting is held every fouryears, the last meeting being held in Beijing as a jointmeeting with the Asian Crystallographic Association(AsCA). Over 650 scientists participated in themeeting.

The keynote speaker was Prof. WayneHendrickson of Columbia University – picturedabove with Prof. James Liu (IBP) – who gave a wellorganized and entertaining history of X-raydiffraction. He also was awarded the prestigiousEinstein Professorship from the Chinese Academy ofSciences.

The program contained a wide range ofcrystallographic topics, including structural biology,small molecule crystallography and material science.

Crystallography in the news

August 1, 2012. A Japanese research team has been investigating how deep seabacteria adapt to such high-pressure conditions. They have identified a structuralchange that confers pressure-resistant properties on a particular protein found inbacteria. Their focus has been on high-pressure protein crystallography, using 3-isopropylmalate dehydrogenase (IPMDH) as a model protein.

August 1, 2012. Researchers are discovering an ever increasing number of proteinsthat perform key cellular tasks without having the fixed, three-dimensional structureonce thought mandatory for a protein to do its job. It is now understood that formany important proteins, or at least for regions of many proteins, the native, functionalstate is unstructured. Those intrinsically disordered proteins (IDPs) defy the structure–function model.

August 2, 2012. Proteins do not need to be surrounded by water to carry out theirvital biological functions, according to scientists from the the Institut Laue Langevinand the Institut de Biologie Structurale (IBS)—both in Grenoble, France—the Universityof Bristol, the Australian National University, and the Forschungszentrum Jülich, inGermany. The team used a state-of-the-art neutron scattering technique todemonstrate that when myoglobin, an oxygen-binding protein found in the muscletissue of vertebrates, is enclosed in a sheath of surfactant molecules, it moves in thesame way as when it is surrounded by water.

August 4, 2012. Researchers have shown how compounds blocking an enzymeuniversal to all influenza viruses may allow development of new antiviral drugs that alsoavoid the problem of drug resistance. Scientists at St. Jude Children's ResearchHospital, led by Prof. Stephen White, have reported details of how certain drugs canprecisely target and inhibit an enzyme essential for the influenza virus's replication. Thestudy has been published online in PLoS Pathogens.

August 10, 2012. Three young group leaders of the Max Planck Institute ofBiochemistry (MPIB) in Martinsried (near Munich) obtained one of the coveted "ERCStarting Grants." Esben Lorentzen, Andreas Pichlmair and Frank Schnorrer will receive€1.5 million each spread over a period of five years for their research projects.

August 20, 2012. Astex Pharmaceuticals, Inc. (Nasdaq: ASTX), a pharmaceuticalcompany dedicated to the discovery and development of novel small moleculetherapeutics, announced that its president and director, Harren Jhoti, PhD, will bepresented with the 2012 Prous Institute-Overton and Meyer Award for NewTechnologies in Drug Discovery by the European Federation for Medicinal Chemistry.

August 21, 2012. A scientific team led by Glenn Butterfoss, and Barney Yoo, researchscientists at New York University, in collaboration with investigators from the U.S.Department of Energy's Lawrence Berkeley National Laboratory (Berkeley Lab), StonyBrook University, and Temple University, have demonstrated that a computer modelingapproach similar to one used to predict protein structures can accurately predictpeptoid conformation as well.

August 22, 2012. The Center for the Advancement of Science in Space (CASIS), thenonprofit organization promoting and managing research on board the InternationalSpace Station (ISS) U.S. National Laboratory, will soon announce two upcoming

solicitations for ISS research proposals. These solicitations follow CASIS' first announcedRFP: "Advancing Protein Crystallization in Microgravity."

August 23, 2012. Internal circadian clocks that are present in nearly every organismand that respond to external cues such as light and temperature are being studied atthe structural biology level by Prof. Brian D. Zoltowski at Southern Methodist University.Zoltowski's lab studies one of the many proteins involved in an organism's circadianclock. Called a photoreceptor, the protein responds to light to predict time of day andseason by measuring day length.

Dr. Na Yang (IBP) & Prof. Jianping Ding (SIBS)

P lateMate mounted on a Rigaku HighF lux HomeLab

Diffraction image from a cry stal in a low profile Greiner plate

New: in-situ screening with Rigaku PlateMate

Introducing the Rigaku PlateMate, a light and non-cumbersome adapter that holds MRCtwo-well and Greiner low-profile crystallization plate types and can be set up on Rigaku4-circle AFC11 partial chi goniometers. The plate slides on horizontal and vertical rails,and accurate positioning is controlled by fine adjustment knobs so crystals in any of the96 wells in the plate can be precisely centered in the X-ray beam.

The PlateMate is an essential tool for easily and rapidly identifying protein crystals versussalt and detergent crystals directly in the plate, and for screening crystals whichdeteriorate as soon as they are taken out of their crystallization environment. Ask formore information.

Lab in the spotlight: Ding Lab

Prof. Jianping DingInstitute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of SciencesShanghai, China

The main research interest of the Ding group is the structuralbiology of regulation of eukaryotic gene expression, which is muchmore complex than in prokaryotes, and involves essentially everystep ranging from the initiation of mRNA synthesis to the endprotein products and occurs at multiple levels, including transcription, exportation, andtranslation.

The Ding group is interested in thestudies of structures, functions, andmolecular mechanisms of a number ofproteins and protein complexesinvolved in the regulation of geneexpression in eukaryotes at variouslevels using structural biology incombination with biochemistry,molecular biology, cell biology, andother biological and biophysicalapproaches. The current ongoing projects focus on the structural and functionalstudies of: (1) proteins involved in epigenetic regulation of eukaryotic genes, such ashistone acetyltransferases and deacetylases, histone methyltransferases anddemethylases, DNA methyltransferases and demethylases, and transcription factors; (2)proteins involved in signaling pathways, particularly the mTOR pathway; (3) importanthuman enzymes involved in protein synthesis and nucleic acid metabolism; (4) antigen-antibody interactions, antibody drugs or potential therapeutic antibodies.

Useful tools for structural biology

The Cambridge Crystallographic Data Centre (CCDC) has compiled the CambridgeStructural Database (CSD) since the 1970s. It is the world's repository of organic andorganometallic crystal structures. They also offer a powerful set of tools for solvingproblems in the drug discovery and life science domains that are used by proteincrystallographers, molecular modelers and medicinal chemists world-wide.

Mogul is a knowledge-based library of molecular geometry derived from the CSD. Itprovides precise information on preferred molecular geometries by enabling access tomillions of chemically classified bond lengths, valence angles, acyclic torsion angles, andring conformations derived from the CSD. Applications of Mogul include ligandrefinement dictionary generation, ligand geometry validation and the testing ofmolecular design ideas.

GOLD is a world-leading docking program that has proven success in virtual screening,lead optimization, and identifying the correct binding mode of active molecules.

Science Video of the Month Prof. David Eisenberg

Harvey Prize Acceptance Lecture

www.y outube.com/watch?v =S7U-nXA Wtv s

Prof. David Eisenberg of University of California atLos Angeles received the Harvey Prize in HumanHealth in recognition of his contribution, pushing thetechnical limits of crystallography, elucidating thestructure of amyloid fibrils. Given the involvement ofamyloid plaques in numerous diseases, includingneurodegenerative disorders, understanding theirstructure has become a central goal of structuralbiology allied to medicine. The ceremony took place onMarch 23, 2009.

Crystallographers in the NewsBirkbeck alum Rob Williams wins Olympic

silver

Birkbeck alum Rob Williams and his GB teammatescame in second in a thrilling rowing showdown at EtonDorney. They took the silver medal in the lightweightmen's four just a quarter of a second behind SouthAfrica. Denmark - the defending champions - camethird despite leading for most of the race. Speaking tothe BBC, Williams said: "It's a tough event. We

lead optimization, and identifying the correct binding mode of active molecules.Comprehensively validated and widely used, it enables users to make confident bindingmode predictions, and achieve high database enrichments. Recent additions to GOLDinclude ensemble docking and new scoring functions.

Relibase+ is a web-based system for the secure storage and in-depth analysis of bothpublic and proprietary structural data. It allows users to easily store and organize theirin-house protein structural data. Furthermore, with its unique search and analysisfunctionality it allows them to quickly come to grips with their protein target, getinspiration for new design ideas, and help assess the risk of cross activity.

More information about what the CCDC offers can be found on their new website,which is currently in trial, so please take a look!

Selected recent crystallographic papers

The Structure of Vimentin Linker 1 and Rod 1B Domains Characterized by Site-directedSpin-labeling Electron Paramagnetic Resonance (SDSL-EPR) and X-ray Crystallography.Aziz, Atya; Budamagunta, Madhu S.; FitzGerald, Paul G.; Hess, John F.; Hunt, John F.;Kuzin, Alexandre P.; Montelione, Gaetano T.; Rong Xiao; Voss, John C.; Yuanpeng J.Huang. Journal of Biological Chemistry. 8/17/2012, Vol. 287 Issue 34, p28349-28361.13p. http://dx.doi.org/10.1074/jbc.M111.334011.

Disease-Associated Polyglutamine Stretches in Monomeric Huntingtin Adopt a CompactStructure. Peters-Libeu, Clare; Miller, Jason; Rutenber, Earl; Newhouse, Yvonne;Krishnan, Preethi; Cheung, Kenneth; Hatters, Danny; Brooks, Elizabeth; Widjaja,Kartika; Tran, Tina; Mitra, Siddhartha; Arrasate, Montserrat; Mosquera, Luis A.; Taylor,Dean; Weisgraber, Karl H.; Finkbeiner, Steven. Journal of Molecular Biology. Aug2012,Vol. 421 Issue 4/5, p587-600. 14p. http://dx.doi.org/10.1016/j.jmb.2012.01.034.

RFCRYS: Sequence-based protein crystallization propensity prediction by means ofrandom forest. Jahandideh, Samad; Mahdavi, Abbas. Journal of Theoretical Biology.Aug2012, Vol. 306, p115-119. 5p. http://dx.doi.org/10.1016/j.jtbi.2012.04.028.

Structural Basis of C-terminal β-Amyloid Peptide Binding by the Antibody Ponezumab forthe Treatment of Alzheimer's Disease. La Porte, Sherry L.; Bollini, Sangeetha Subbarao;Lanz, Thomas A.; Abdiche, Yasmina N.; Rusnak, Alexander S.; Ho, Wei-Hsien;Kobayashi, Dione; Harrabi, Ons; Pappas, Danielle; Mina, Erene W.; Milici, Anthony J.;Kawabe, Thomas T.; Bales, Kelly; Lin, John C.; Pons, Jaume. Journal of MolecularBiology. Aug2012, Vol. 421 Issue 4/5, p525-536. 12p.http://dx.doi.org/10.1016/j.jmb.2011.11.047.

Membrane protein structure determination by electron crystallography. Ubarretxena-Belandia, Iban; Stokes, David L. Current Opinion in Structural Biology. Aug2012, Vol. 22Issue 4, p520-528. 9p. http://dx.doi.org/10.1016/j.sbi.2012.04.003.

A gradual desiccation method for improving the efficiency of protein crystallizationscreening. Lu, Qin-Qin; Xie, Xu-Zhuo; Chen, Rui-Qing; Wu, Zi-Qing; Cheng, Qing-Di;Shang, Peng; Yin, Da-Chuan. Journal of Applied Crystallography. Aug2012, Vol. 45Issue 4, p758-765. 8p. http://dx.doi.org/10.1107/S0021889812025757.

Structural Determinants of the β-Selectivity of a Bacterial Aminotransferase. Wybenga,Gjalt G.; Crismaru, Ciprian G.; Janssen, Dick B.; Dijkstra, Bauke W. Journal of BiologicalChemistry. 8/17/2012, Vol. 287 Issue 34, p28495-28502. 8p.http://dx.doi.org/10.1074/jbc.M112.375238.

Fine-needle capillary mounting for protein microcrystals. Makino, Masatomo; Wada,Izumi; Mizuno, Nobuhiro; Hirata, Kunio; Shimizu, Nobutaka; Hikima, Takaaki; Yamamoto,Masaki; Kumasaka, Takashi. Journal of Applied Crystallography. Aug2012, Vol. 45 Issue4, p785-788. 4p. http://dx.doi.org/10.1107/S0021889812024545.

Tetrameric Structure of the GlfT2 Galactofuranosyltransferase Reveals a Scaffold forthe Assembly of Mycobacterial Arabinogalactan. Wheatley, Robert W.; Zheng, RuixiangBlake; Richards, Michele R.; Lowary, Todd L.; Ng, Kenneth K. S. Journal of BiologicalChemistry. 8/10/2012, Vol. 287 Issue 33, p28132-28143. 12p.http://dx.doi.org/10.1074/jbc.M112.347484.

MobiDB: a comprehensive database of intrinsic protein disorder annotations. DiDomenico, Tomás; Walsh, Ian; Martin, Alberto J.M.; Tosatto, Silvio C.E. Bioinformatics.Aug2012, Vol. 28 Issue 15, p2080-2081. 2p.http://dx.doi.org/10.1093/bioinformatics/bts327.

the BBC, Williams said: "It's a tough event. Wewanted to win. We have to be happy to get a medalat our home Olympics. It's a shame we didn't win, butwhat can you do? We did everything we could."

Williams and his GB teammates won their Olympicsemi-final on Tuesday and their first heat on theopening day of competition on Saturday. They alsowon the World Cup competition in Munich in June.Williams recently finished his PhD in crystallography atBirkbeck and UCL's Institute of Structural andMolecular Biology. He studied full-time in the winterand part-time in the summer to enable him to trainand compete.

Professor Nicholas Keep, Executive Dean of Birkbeck'sSchool of Science, said: "Congratulations to Rob - awonderful performance. He shows the samededication and excellence in his science."

Survey of the Month

http://www.surveymonkey.com/s/rigakusurvey

June Survey Results

If you had to categorize your spam messages, whichcategory best fits what you mostly receive?

http://dx.doi.org/10.1093/bioinformatics/bts327.

Atomic structure of the vimentin central α-helical domain and its implications forintermediate filament assembly. Chernyatina, Anastasia A.; Nkolet, Stefan; Aebi, Ueli;Herrmann, Harald; Strelkov, Sergei V. Proceedings of the National Academy of Sciencesof the United States of America. 8/21/2012, Vol. 109 Issue 34, p13620-13625. 6p.http://dx.doi.org/10.1073/pnas.1206836109.

Relaxosome function and conjugation regulation in F-like plasmids - a structural biologyperspective. Wong, Joyce J. W.; Lu, Jun; Glover, J. N. Mark. Molecular Microbiology.Aug2012, Vol. 85 Issue 4, p602-617. 16p. 5 Diagrams.http://dx.doi.org/10.1111/j.1365-2958.2012.08131.x.

Atypical ubiquitylation - the unexplored world of polyubiquitin beyond Lys48 and Lys63linkages. Kulathu, Yogesh; Komander, David. Nature Reviews Molecular Cell Biology.Aug2012, Vol. 13 Issue 8, p508-523. 16p. 6 Diagrams.http://dx.doi.org/10.1038/nrm3394.

Transformation of the dihedral corrective map for d-amino residues using the CHARMMforce field. Turpin, Eleanor R.; Hirst, Jonathan D. Chemical Physics Letters. Aug2012,Vol. 543, p142-147. 6p. http://dx.doi.org/10.1016/j.cplett.2012.06.041.

Electron crystallography — the waking beauty of structural biology. Pope, ChristopherR; Unger, Vinzenz M. Current Opinion in Structural Biology. Aug2012, Vol. 22 Issue 4,p514-519. 6p. http://dx.doi.org/10.1016/j.sbi.2012.03.006.

Scaffoldin Conformation and Dynamics Revealed by a Ternary Complex from theClostridium thermocellum Cellulosome. Currie, Mark A.; Adams, Jarrett J.; Faucher,Frédérick; Bayer, Edward A.; Jia, Zongchao; Smith, Steven P. Journal of BiologicalChemistry. 8/3/2012, Vol. 287 Issue 32, p26953-26961. 9p.http://dx.doi.org/10.1074/jbc.M112.343897.

Highlights from recently determined structures of membrane proteins: a focus onchannels and transporters. Sciara, Giuliano; Mancia, Filippo. Current Opinion in StructuralBiology. Aug2012, Vol. 22 Issue 4, p476-481. 6p.http://dx.doi.org/10.1016/j.sbi.2012.03.005.

Significant reduction in errors associated with nonbonded contacts in protein crystalstructures: automated all-atom refinement with PrimeX. Bell, Jeffrey A.; Ho, KennethL.; Farid, Ramy. Acta Crystallographica: Section D. Aug2012, Vol. 68 Issue 8, p935-952.18p. http://dx.doi.org/10.1107/S0907444912017453.

Book review:

Visual Strategies: A Practical Guide to Graphics for Scientists and Engineers

by Felice C. Frankel and Angela H. DePace Yale University Press, 2012; ISBN: 0300176449, 9780300176445

I saw a review of this book in Nature and picked up a copy for myself. The authors setout to provide a modern guidebook for improving the transmission of scientificinformation to other scientists and non-scientists. Edward R. Tufte has done thisbefore, but this book considers the latest tools of the trade and so should become acompanion to, or even a replacement for, the Quantitative Display of Information.

The book is divided into eight tabbed sections. The tabs are designed to allow one togo to a particular section quickly. The first tab is the Overview and includes aninterview with the authors and Stephan Stagmeister, the book's designer. The authorsintroduce three questions that should be asked of every graphic:

1. Is the graphic explanatory or exploratory? 2. How will the graphic be used? 3. What is the first thing you want the viewer to see?

The authors next describe five steps to designing a graphic: compose, abstract, color,layer and refine. These steps are reviewed for a number of examples provided in theOverview. The next three chapters (tabs) cover the topics Form and Structure,Process and Time, and Compare and Contrast — with before and after examplesshowing how to improve a particular graphic. The Form and Structure section providestwo examples relevant to structural biology. All three chapters provide examples forbiology, chemistry, physics and medicine.

The Case Studies chapter takes a long look at developing a particular graphic from theground up by an expert in the field. Jane Richardson provides the example tit led

"Representing Folded Proteins." The last chapter, Interactive Graphics, describes indetail how one may employ web-based tools to enhance a graphic that would be toohard to make easily understandable only on paper. The structural biology example is"The Ribosome in Animation" and was created by Said Sannuga. This example is notreally interactive but shows the power of modern tools for describing complexprocesses. The penultimate tab is a Visual Index so that one may quickly locate aparticular example by its graphic. The final tab is an appendix of references andresources.

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

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