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Protein Crystallography NewsletterVolume 4, No. 5, May 2012
In this issue:
Crystallography in the news
Science video of the month
Product spotlight: Compact HomeLab
Spotlight: Southampton Diffraction Centre
Useful links for crystallography
Crystallographers in the news
Selected recent crystallographic papers
Funny video of the month
Survey of the month
Book review
Science Video of the Month
iBioSeminar by Prof. Stephen Harrison (pt. 2)
http://www.y outube.com/watch?v =qcepGv FUM38
Harrison begins his talk by asking why most non-enveloped viruses and some enveloped viruses aresymmetrical in shape. He proceeds to show us lovelyimages of the structures obtained by X-ray crystallo-graphy of numerous viral coat proteins. Decipheringthese structures allowed scientists to understand thatviral coat proteins form multimers, such as dimers andpentamers, which in turn interact with a scaffold thatensures that the coat proteins, are correctly placed.This arrangement results in symmetrically shapedviruses.
In Part 1 (last month's featured video), Harrison alsoexplains that enveloped viruses infect cells by inducingthe fusion of the viral and host cell membranes. He
delves deeper into the molecular mechanism of mem-brane fusion driven by the hemagglutinin (or HA) proteinof the influenza virus in Part 2 of his talk. Non-enveloped viruses, on the other hand, must enter cells
Crystallography in the news
May 7, 2012. Zenobia Therapeutics, Inc., a leader in fragment-based lead discovery(FBLD) for CNS diseases and FBLD/structural biology services, and BioBlocks, Inc.(BioBlocks), a leader in medicinal chemistry services and novel building block products,announced today that they are adding a 284 compound fragment library to theirproduct offerings.
May 9, 2012. Mitegen LLC, a provider of innovative consumables for X-ray diffraction,crystallography and protein crystallization to academic, pharmaceutical, industrial andgovernment researchers around the world, recently announced consolidation andimprovements to its MicroLoops™ and MicroLoops™ HT product lines of crystal mountsfor X-ray crystallography.
May 11, 2012. A detailed study of the crystal structure of Poly(ADP-ribose)polymerase-1 (PARP-1) complexed with a double-stranded DNA break by researchers atThomas Jefferson University's Kimmel Cancer Center has identified specific domains onthe enzyme that could represent targets for the design of more specific PARP-1inhibitors. PARP-1 is a protein that detects and responds to DNA breaks. Inhibitorstargeting the enzyme are being tested in anticancer trials.
May 21, 2012. Drug maker Takeda will close the South San Francisco site it oncetagged as a key to developing early stage antibody drugs. The Japanese company saidit is consolidating its South San Francisco and San Diego operations, now called TakedaCalifornia, in San Diego. The San Diego site will combine protein X-ray crystallography,small molecule, antibody and antibody-drug conjugate work targeting cancer,inflammatory diseases and metabolic diseases.
May 22, 2012. One of the most important structures in a cell is the nuclear porecomplex—a tiny yet complicated channel through which information flows in and out ofthe cell's nucleus, directing all other cell activity. Massachusetts Institute of Technologybiologist Thomas Schwartz is using X-ray crystallography to steadily assemble athorough portrait of the 500 proteins that make up nuclear pores and how they cometogether to perform their crucial role.
May 22, 2012. Johns Hopkins scientists have discovered a protein that appears toplay an important regulatory role in deciding whether stem cells differentiate into thecells that make up the brain, as well as countless other tissues. "Notch signaling isinvolved in almost all aspects of tissue development," explains study leader ValinaDawson, Ph.D., a professor in the departments of Neurology, Neuroscience, andPhysiology and co-director of the Stem Cell and Neuroregeneration Programs at theInstitute for Cell Engineering at the Johns Hopkins University School of Medicine.
May 23, 2012. Weill Cornell Medical College researchers, led by Dr. Mark A. Rubin, TheHomer T. Hirst Professor of Oncology in Pathology and vice chair for experimentalpathology, have found that a chromosomal mutation likely contributes to earlydevelopment of prostate cancer — and suggests a model for how other chromosomaltranslocations, common to many tumor types, are linked to cancer formation andgrowth.
May 23, 2012. Biotech drugmaker Amgen Inc. has introduced new CEO Bob Bradwayto shareholders at the company's annual meeting, with retiring CEO Kevin Sharerstepping down after a decade.
May 24, 2012. Oregon State University biophysicist Andy Karplus and his colleagueKay Diederichs at the University of Konstanz in Germany have now proven that usefulinformation can be gleaned from crystallographic data that has about five times the
noise level than was previously considered acceptable.
May 28, 2012. Faculty appointments are key to arresting the decline of stateuniversities. The case of the Department of Crystallography and Biophysics at Madras
by a mechanism other than membrane fusion. This is thefocus of Part 3. Using rotavirus as a model, Harrison andhis colleagues have used a combination of X-raycrystallography and electron cryomicroscopy to decipherhow the spike protein on the viral surface changes itsconformation and perforates the cell membrane allowingthe virus to enter the cell.
Product spotlight: Compact HomeLab
C ompact HomeLab
Crystallographers in the News
Team wins prestigious global award for cancerdrug success
A multidisciplinary team from The Institute of CancerResearch (ICR) and The Royal Marsden Hospital, whichreceives funding from Cancer Research UK, has won a
universities. The case of the Department of Crystallography and Biophysics at MadrasUniversity is described.
Product spotlight: Compact HomeLab
Rigaku's new Compact HomeLab was designed for structural biologists who want a low-maintenance X-ray system that is easy to use, and provides the ultimate in experimen-tal flexibility. From screening crystals prior to a synchrotron trip to solving structuresfrom SAD phasing, the Compact HomeLab provides your group with the tools it needsto carry out structural biology in today's fast and competitive environment.
Rigaku's Compact HomeLab brings a new level of capabilit ies for protein crystallographyto your lab. It has the industry's highest usable flux from a micro-focus sealed tube X-ray source, a comforting three year tube warranty, a new high-gain CCD detector,remote iPad or iPhone control and monitoring, and the unparalleled performance ofHKL-3000R instrument control, data processing and structure solution software. TheCompact HomeLab gives you everything you need to properly screen crystals inadvance of a synchrotron experiment or teach your students the science of solvingprotein structures. Ask for more information.
Lab in the spotlight: Southampton Diffraction Centre
Southampton Diffraction Centre (SDC)Dr. Simon Coles, DirectorChemical and Life Sciences: Bridging the gap
The vision of the SDC is one of a fully integrated structure-centric research facilitywhere chemists and life scientists work together and learn from each other to progressindividual research projects and the field as a whole.
The SDC is an organization that pools facilit ies and services associated with the analysisof atomic resolution structure from both the Chemical and Life Sciences. The centerboasts state-of-the-art instrumentation and exceptional expertise in crystallization,diffraction and thermal analysis of both small and macromolecular-based systems. TheUK National Crystallography Service, funded by EPSRC, is housed within the centre andprovides a centralized service for chemistry-based academia where advanced facilit iesare required to answer problems that cannot be solved with local resources.Additionally, our exceptional facilit ies are accessible to industrial-based research throughSouthampton Chemistry Analytical Solutions.
Useful link - new refinement software
Scientists at the University of Chicago have developedautomated software to refine crystallographic, EM, and NMRstructures. The server converts moderate- to low-resolutionstructures at initial (e.g., backbone trace only) or late stages ofrefinement to structures with increased numbers of hydrogenbonds, improved crystallographic R-factors, and superiorbackbone geometry. The fully automated method is applicable toDNA-binding and membrane proteins of any size and will aidstudies of structural biology by improving model quality and savingconsiderable effort. It can be applied to the entire structure orjust specific regions, and employed multiple times in conjunction with other refinementtools. It can be used with or without electron density and is available on the GodzillaComputing Cluster. Ref. Haddadian, et al. (2011). Automated real-space refinement ofprotein structures using a realistic backbone move set. Biophys. J.101, 899. The
method was used in Krishnamurthy, H. & Gouaux, E. (2012) Nature 481, p469; Scharfet al. (2010) Immunity 33, p853; Feld et al. (2010) Nat Struct Mol Biol 17, p1383.
Selected recent crystallographic papers
receives funding from Cancer Research UK, has won a
prestigious global award for its success in taking newcancer drugs from concept to patients.
This is the first time the American Association for CancerResearch (AACR) Team Science Award has been wonoutside the US. The AACR said its decision was based on"the tremendous impact this team has had in preclinicaland clinical studies of cancer therapeutics."
The Team members are from the Cancer Research UKCancer Therapeutics Unit at the ICR, which discoversnew drugs, and the Drug Development Unit at the ICRand The Royal Marsden, which progresses drugcandidates into clinical trials.
Funny Video of the Month
Sh*t NCSU Biochemistry Grad Students Say
http://www.y outube.com/watch?v =jBclO dmfpMU
Survey of the Month
http://www.surveymonkey.com/s/5_12
April Survey Results
Structural biology is such an international field that thereare essentially no geographical boundaries. This meansthat many structural biologists travel on a global basis toattend scientific meetings and visit colleagues. What isyour favorite way to pass the time on an international
flight?
Selected recent crystallographic papers
Automatic prediction of flexible regions improves the accuracy of protein-proteindocking models. Luo, Xiaohu; Lü, Qiang; Wu, Hongjie; Yang, Lingyun; Huang, Xu; Qian,Peide; Fu, Gang. Journal of Molecular Modeling, May2012, Vol. 18 Issue 5, p2199-2208, 10p; http://dx.doi.org/10.1007/s00894-011-1231-0
The structure of Ca2+-loaded S100A2 at 1.3-Å resolution. Koch, Michael; Fritz, Günter.FEBS Journal, May2012, Vol. 279 Issue 10, p1799-1810, 12p;http://dx.doi.org/10.1111/j.1742-4658.2012.08556.x
Computational design of a protein crystal. Lanci, Christopher J.; MacDermaid,Christopher M.; Kang, Seung-gu; Acharya, Rudresh; North, Benjamin; Xi Yang; Qiu, X.Jade; DeGrado, William F.; Saven, Jeffery G. Proceedings of the National Academy ofSciences of the United States of America, 5/8/2012, Vol. 109 Issue 19, p7304-7309,6p; http://dx.doi.org/10.1073/pnas.1112595109
Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and52. Gopalakrishnan, Ranganath; Kozany, Christian; Wang, Yansong; Schneider, Sabine;Hoogeland, Bastiaan; Bracher, Andreas; Hausch, Felix. Journal of Medicinal Chemistry,May2012, Vol. 55 Issue 9, p4123-4131, 9p; http://dx.doi.org/10.1021/jm201747c
X-ray crystallographic structure-based design of selective thienopyrazole inhibitors forinterleukin-2-inducible tyrosine kinase. McLean, Larry R.; Zhang, Ying; Zaidi, Nisha; Bi,Xiping; Wang, Rachel; Dharanipragada, Ram; Jurcak, John G.; Gillespy, Timothy A.;Zhao, Zhicheng; Musick, Kwon Y.; Choi, Yong-Mi; Barrague, Matthieu; Peppard, Jane;Smicker, Matthew; Duguid, Mei; Parkar, Ashfaq; Fordham, Jeremy; Kominos, Dorothea.Bioorganic & Medicinal Chemistry Letters, May2012, Vol. 22 Issue 9, p3296-3300, 5p;http://dx.doi.org/10.1016/j.bmcl.2012.03.016
Sensitivity of lysozyme crystallization to minute variations in concentration. Chen, Rui-Qing; Yin, Da-Chuan; Lu, Qin-Qin; Shi, Jian-Yu; Ma, Xiao-Liang. Acta Crystallographica:Section D, May2012, Vol. 68 Issue 5, p584-591, 8p;http://dx.doi.org/10.1107/S0907444912006427
In situ macromolecular crystallography using microbeams. Axford, Danny; Owen, RobinL.; Aishima, Jun; Foadi, James; Morgan, Ann W.; Robinson, James I.; Nettleship, JoanneE.; Owens, Raymond J.; Moraes, Isabel; Fry, Elizabeth E.; Grimes, Jonathan M.; Harlos,Karl; Kotecha, Abhay; Ren, Jingshan; Sutton, Geoff; Walter, Thomas S.; Stuart, DavidI.; Evans, Gwyndaf. Acta Crystallographica: Section D, May2012, Vol. 68 Issue 5,p592-600, 9p; http://dx.doi.org/10.1107/S0907444912006749
Holding back the microfilament—Structural insights into actin and the actin-monomer-binding proteins of apicomplexan parasites. Olshina, Maya A.; Wong, Wilson; Baum,Jake. IUBMB Life, May2012, Vol. 64 Issue 5, p370-377, 8p, 2 Diagrams;http://dx.doi.org/10.1002/iub.1014
Dynein dynamics. Höök, Peter; Vallee, Richard. Nature Structural & Molecular Biology,May2012, Vol. 19 Issue 5, p467-469, 3p; http://dx.doi.org/10.1038/nsmb.2290
Structure and stoichiometry of an accessory subunit TRIP8b interaction withhyperpolarization-activated cyclic nucleotide-gated channels. Bankston, John R.; Camp,Stacey S.; DiMaio, Frank; Lewis, Alan S.; Chetkovich, Dane M.; Zagotta, William N.Proceedings of the National Academy of Sciences of the United States of America,5/15/2012, Vol. 109 Issue 20, p7899-7904, 6p;http://dx.doi.org/10.1073/pnas.1201997109
X-ray-excited optical luminescence of protein crystals: a new tool for studying radiationdamage during diffraction data collection. Owen, Robin L.; Yorke, Briony A.; Pearson,Arwen R. Acta Crystallographica: Section D, May2012, Vol. 68 Issue 5, p505-510, 6p;http://dx.doi.org/10.1107/S0907444912002946
Rapid-access, high-throughput synchrotron crystallography for drug discovery.
Wasserman, Stephen R.; Koss, John W.; Sojitra, Sonal T.; Morisco, Laura L.; Burley,Stephen K. Trends in Pharmacological Sciences, May2012, Vol. 33 Issue 5, p261-267,7p; http://dx.doi.org/10.1016/j.tips.2012.03.009
Efficiency of detergents at maintaining membrane protein structures in their biologicallyrelevant forms. Tulumello, David V.; Deber, Charles M. BBA - Biomembranes, May2012,Vol. 1818 Issue 5, p1351-1358, 8p;http://dx.doi.org/10.1016/j.bbamem.2012.01.013
Substrate selectivity of drug-metabolizing cytochrome P450s predicted from crystalstructures and in silico modeling. Dong, Dong; Wu, Baojian; Chow, Diana; Hu, Ming.Drug Metabolism Reviews, May2012, Vol. 44 Issue 2, p192-208, 17p;
Drug Metabolism Reviews, May2012, Vol. 44 Issue 2, p192-208, 17p;http://dx.doi.org/10.3109/03602532.2011.645580
Atomic structure of the autosomal recessive hypercholesterolemia phosphotyrosine-binding domain in complex with the LDL-receptor tail. Dvir, Hay; Shah, Mehul; Girardi,Enrico; Guo, Lixia; Farquhar, Marilyn G.; Zajonc, Dirk M. Proceedings of the NationalAcademy of Sciences of the United States of America, 5/1/2012, Vol. 109 Issue 18,p6916-6921, 6p; http://dx.doi.org/10.1073/pnas.1114128109
Crystal structure of Cwc2 reveals a novel architecture of a multipartite RNA-bindingprotein. Schmitzová, Jana; Rasche, Nicolas; Dybkov, Olexander; Kramer, Katharina;Fabrizio, Patrizia; Urlaub, Henning; Lührmann, Reinhard; Pena, Vladimir. EMBO Journal,5/2/2012, Vol. 31 Issue 9, p2222-2234, 13p;http://dx.doi.org/10.1038/emboj.2012.58
Notes of a protein crystallographer: on the high-resolution structure of the PDB growthrate. Abad-Zapatero, Cele. Acta Crystallographica: Section D, May2012, Vol. 68 Issue5, p613-617, 5p; http://dx.doi.org/10.1107/S0907444912004799
Novel β-structure of YLR301w from Saccharomyces cerevisiae. Kim, Kook-Han; Ahn,Hyung Jun; Lee, Won-Kyu; Lee, Cheolju; Yu, Myeong-Hee; Kim, Eunice EunKyeong.Acta Crystallographica: Section D, May2012, Vol. 68 Issue 5, p531-540, 10p;http://dx.doi.org/10.1107/S090744491200491X
Peptide inhibitors of botulinum neurotoxin serotype A: design, inhibition, cocrystalstructures, structure-activity relationship and pharmacophore modeling. Kumar,Gyanendra; Kumaran, Desigan; Ahmed, S. Ashraf; Swaminathan, Subramanyam. ActaCrystallographica: Section D, May2012, Vol. 68 Issue 5, p511-520, 10p;http://dx.doi.org/10.1107/S0907444912003551
Book review:
Packing for Mars: The Curious Science of Life in the Void by Mary Roach W. W. Norton & Company (2010), ISBN-13: 978-0393068474
In her nonfiction book, Packing for Mars, Mary Roach explores the numerous (andoften less mainstream) trials and tribulations astronauts in training must undergo beforethey achieve clearance for travel to outer space.
Roach's book is chock-full of interesting tidbits of information about NASA and itspractices and policies. Roach balances sometimes overwhelming ideas with anecdotalfootnotes and a witty, deadpan sense of humor. The ideas themselves are notoverwhelming conceptually, but rather overwhelming to the senses. For example, anentire chapter is dedicated to discussing the difficulties and dilemmas of liquid and solidexcretion in zero gravity. Roach exhibits an acute attention to detail and anunparalleled inquisitiveness as she digs into the past, present, and future of spacetravel. Additionally, the book is a fast-paced and energetic read, a means for thosewith litt le or no knowledge or experience in extraterrestrial affairs to learn a lot.
Among the topics Roach delves into are: the procedures by which potential Japaneseastronauts are assessed and tested for desirable qualit ies by JAXA (the Japaneseequivalent of NASA), both in intellect and personality (think solitary confinement and1000 origami paper cranes, each methodologically analyzed for signs of psychologicaldeterioration in the test subject); the psychology of isolation and confinement, or howNASA attempts to assess how the human brain reacts to extended periods of forcedasocial conditions; the effects of space travel on the psyche, or how a number of
former astronauts (think Lisa Nowak) have exhibited signs of mental instability following"out of this world" ventures; the dangers of life in zero gravity and the perpetualplague of motion sickness that afflicts many astronauts-in-training and even those whomake it to the Moon (Roach does debunk the myth that barfing in a spacesuit willresult in death by vomit; astronauts are not supposed to be intoxicated, as Jimi Hendrixwas); the careers of two space chimps, Ham and Enos, who were only two of themany non-human mammalian test subjects used for assessing the effects of spacetravel on the human body; and the nausea-inducing nature of freeze-dried cuisine(tomato paste anyone?) and other aerospace delicacies (corned beef sandwiches +zero gravity= crumb snowstorm). This is not an exhaustive list, merely a glimpse of thebreadth and wealth of material Roach covers in her work.
Perhaps my favorite anecdote is that of the NASA crash test dummy. Unlike thecreepy mannequins from car commercials, the National Aeronautics and SpaceAdministration uses cadavers. They are frozen after death, and thawed for several daysprior to testing. These cadavers are used to provide more accurate information
Mary Roach
prior to testing. These cadavers are used to provide more accurate informationconcerning the effects of higher G forces applied laterally, longitudinally, andtransversely. It is difficult to simulate the effects of a human body in a crash on amannequin because of the intricacies of organ placement in the abdominal cavity. Also,one of the most important things to study in a crash test is the effect of the crash onthe brain (which mannequins do not possess).
All in all, Packing for Mars is an engaging and enjoyable read, appropriate for scienceenthusiasts and other people of a curious nature.
Jeanette S. Ferrara Princeton, Class of 2015
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