Crystallography in the news

November 1, 2013. A postdoctoral position is available for a highly motivated individual at the Department of Medical Biochemistry & Biophysics, Karolinska Institutet, Stockholm, Sweden. The candidate will join ongoing multidisciplinary research aimed at the structural and functional characterization of proteins and protein complexes from major pathogens.

November 5, 2013. Paul Adams, a bioengineer with Berkeley Lab's Physical Biosciences Division, and a team that included the research group of David Baker at the University of Washington, have developed a new method for refining crystallographic data that combines aspects of PHENIX with aspects of Rosetta, the most widely used software for the prediction and design of the three-dimensional structure of proteins and other large biomolecules.

November 7, 2013. The U.S. National Science Foundation committed $25 million for a Science and Technology Center based at the University at Buffalo to explore the use of strong X-ray lasers to detail the atomic structures of molecules with a resolution approaching the nanoscale. The grant will be used to establish the BioXFEL research center to focus on developing new X-ray bioimaging techniques - including an advanced form of X-ray crystallography called serial femtosecond crystallography.

November 8, 2013.  A cellular pathway interaction known as TWEAK-Fn14, often associated with repair of acute injuries, also is a viable target for drug therapy that could prevent the spread of cancer, especially brain cancer, according to a study led by the Translational Genomics Research Institute (TGen). TWEAK is a cytokine, or soluble protein, that controls many cellular activities and acts by binding to a cell surface receptor known as Fn14.

November 18, 2013. Researchers at The Scripps Research Institute (TSRI) have now solved the structure of a key protein in the Nipah virus, which could pave the way for the development of a much-needed antiviral drug. The Nipah virus is an emerging pathogen found in Southeast Asia, with the first outbreak in 1997.

November 19, 2013. The National Institute of Allergy and Infectious Diseases (NIAID) has awarded the University of Chicago $4.4 million over five years to study genes of unknown function in bacteria that cause plague and brucellosis. Sean Crosson, PhD, associate professor of biochemistry and molecular biophysics will lead the effort to characterize hypothetical genes -- genes revealed via genome sequencing that as yet have no defined functional role -- as part of a new Functional Genomics program at the NIAID.

November 20, 2013.  A new technique has been used to solve protein crystal structures on a much smaller scale than done before. A team at the Howard Hughes Medical Institute, led by Tamir Gonen, has used cryo-electron microscopy to do electron diffraction on microcrystals of lysozyme protein.

November 22, 2013. CMDBioscience Inc., a pioneering innovator in peptide drug design and computational modeling, announced the appointment of Tomi Sawyer, Ph.D., as the founding chair of its Scientific Advisory Board. Dr. Sawyer joins Victor Hruby, Ph.D., Bernhardt Trout, Ph.D., Benjamin Wolozin, Ph.D., and Yaoqi Zhou, Ph.D. as founding members of the Scientific Advisory Board.

Product spotlight: CrystalMation

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Images at right are of a recent installation of a CrystalMation system at Dart Neurosciences.

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The SGC (Structural Genomics Consortium) is a not-for-profit, public-private partnership with the directive to carry out basic science of relevance to drug discovery. The core mandate of the SGC is to determine 3D structures on a large scale and cost-effectively - targeting human proteins of biomedical importance and proteins from human parasites that represent potential drug targets. As of May 2013, the SGC is responsible for >10% of all novel human protein structures deposited into the Protein Data Bank each year; through May 2013 the SGC has released almost 1500 structures of proteins with implications to the development of new therapies for cancer, diabetes, obesity, and psychiatric disorders.

Frank has been head of the PX group since the start of the SGC in 2004; in late 2012 he also joined Diamond synchrotron as head of beamline I04-1. He is focused on methodology and high throughput techniques for crystallography.

The PX group is a joint research effort with Diamond's beamline I04-1: they are revisiting fragment screening by crystal structure, by making medium throughput soaking and X-ray structure a routine experiment. For I04-1, the ambition is to set this up as part of Diamond's user program; and the long goal is to establish how protein structures can become routine, predictive and thus essential tools for guiding medicinal chemistry - as opposed to their current usual role as occasional, descriptive, and generally merely nice-to-have data points.

GPCRDB: information system for G protein-coupled receptors. The GPCRDB is a molecular-class information system that collects, combines, validates and stores large amounts of heterogeneous data on G protein-coupled receptors (GPCRs). The GPCRDB contains data on sequences, ligand binding constants and mutations. In addition, many different types of computationally derived data are stored such as multiple sequence alignments and homology models. The GPCRDB is designed to be a data storage medium, as well as a tool to aid biomedical scientists with answering questions by offering a single point of access to many types of data that are integrated and visualized in a user-friendly way.

Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory Syncytial Virus. McLellan, Jason S.; Chen, Man; Joyce, M. Gordon; Sastry, Mallika; Stewart-Jones, Guillaume B. E.; Yongping Yang; Baoshan Zhang; Lei Chen; Srivatsan, Sanjay; Anqi Zheng; Tongqing Zhou; Graepel, Kevin W.; Kumar, Azad; Moin, Syed; Boyington, Jeffrey C.; Gwo-Yu Chuang; Soto, Cinque; Baxa, Ulrich; Bakker, Arjen Q.; Spits, Hergen. Science. 11/1/2013, Vol. 342 Issue 6158, p592-598. 7p. http://dx.doi.org/10.1126/science.1243283.

JAXA protein crystallization in space: ongoing improvements for growing high-quality crystals. Takahashi, Sachiko; Ohta, Kazunori; Furubayashi, Naoki; Yan, Bin; Koga, Misako; Wada, Yoshio; Yamada, Mitsugu; Inaka, Koji; Tanaka, Hiroaki; Miyoshi, Hiroshi; Kobayashi, Tomoyuki; Kamigaichi, Shigeki. Journal of Synchrotron Radiation. Nov2013, Vol. 20 Issue 6, p968-973. 6p. http://dx.doi.org/10.1107/S0909049513021596.

SCEDS: protein fragments for molecular replacement in Phaser.  McCoy, Airlie J.; Nicholls, Robert A.; Schneider, Thomas R. Acta Crystallographica: Section D. Nov2013, Vol. 69 Issue 11, p2216-2225. 10p. http://dx.doi.org/10.1107/S0907444913021811.

Crystallographic Analysis of the Reaction Cycle of 2',3'-Cyclic Nucleotide 3'-Phosphodiesterase, a Unique Member of the 2H Phosphoesterase Family. Myllykoski, Matti; Raasakka, Arne; Lehtimäki, Mari; Han, Huijong; Kursula, Inari; Kursula, Petri. Journal of Molecular Biology. Nov2013, Vol. 425 Issue 22, p4307-4322. 16p. http://dx.doi.org/10.1016/j.jmb.2013.06.012.

Solution Small Angle X-ray Scattering (SAXS) Studies of RecQ from Deinococcus radiodurans and Its Complexes with Junction DNA Substrates. Wenjia Wang; Haifeng Hou; Qian Du; Wen Zhang; Guangfeng Liu; Shtykova, Eleonora V.; Jianhua Xu; Peng Liu; Yuhui Dong. Journal of Biological Chemistry. 11/8/2013, Vol. 288 Issue 45, p32414-32423. 10p. http://dx.doi.org/10.1074/jbc.M113.502112.

Sub-millisecond time-resolved SAXS using a continuous-flow mixer and X-ray microbeam. Graceffa, Rita; Nobrega, R. Paul; Barrea, Raul A.; Kathuria, Sagar V.; Chakravarthy, Srinivas; Bilsel, Osman; Irving, Thomas C. Journal of Synchrotron Radiation. Nov2013, Vol. 20 Issue 6, p820-825. 6p. http://dx.doi.org/10.1107/S0909049513021833.

Transient tertiary structures in tau, an intrinsically disordered protein. Battisti, Anna; Ciasca, Gabriele; Tenenbaum, Alexander. Molecular Simulation. Nov2013, Vol. 39 Issue 13, p1084-1092. 9p. http://dx.doi.org/10.1080/08927022.2013.794275.

Unanswered questions about the structure of cytochrome bc1 complexes. Berry, Edward A.; De Bari, Heather; Huang, Li-Shar. BBA - Bioenergetics. Nov2013, Vol. 1827 Issue 11/12, p1258-1277. 20p. http://dx.doi.org/10.1016/j.bbabio.2013.04.006.

Phase-diagram-guided method for growth of a large crystal of glycoside hydrolase family 45 inverting cellulase suitable for neutron structural analysis. Nakamura, Akihiko; Ishida, Takuya; Fushinobu, Shinya; Kusaka, Katsuhiro; Tanaka, Ichiro; Inaka, Koji; Higuchi, Yoshiki; Masaki, Mika; Ohta, Kazunori; Kaneko, Satoshi; Niimura, Nobuo; Igarashi, Kiyohiko; Samajima, Masahiro. Journal of Synchrotron Radiation. Nov2013, Vol. 20 Issue 6, p859-863. 5p. http://dx.doi.org/10.1107/S0909049513020943.

Unlocking the secrets of the gatekeeper: Methods for stabilizing and crystallizing GPCRs. Bertheleme, Nicolas; Chae, Pil Seok; Singh, Shweta; Mossakowska, Danuta; Hann, Michael M.; Smith, Kathrine J.; Hubbard, Julia A.; Dowell, Simon J.; Byrne, Bernadette. BBA - Biomembranes. Nov2013, Vol. 1828 Issue 11, p2583-2591. 9p. http://dx.doi.org/10.1016/j.bbamem.2013.07.013.

IgG2 Fc structure and the dynamic features of the IgG CH2-CH3 interface. Teplyakov, Alexey; Zhao, Yonghong; Malia, Thomas J.; Obmolova, Galina; Gilliland, Gary L. Molecular Immunology. Nov2013, Vol. 56 Issue 1/2, p131-139. 9p. http://dx.doi.org/10.1016/j.molimm.2013.03.018.

From lows to highs: using low-resolution models to phase X-ray data. Stuart, David I.; Abrescia, Nicola G. A. Acta Crystallographica: Section D. Nov2013, Vol. 69 Issue 11, p2257-2265. 9p. http://dx.doi.org/10.1107/S0907444913022336.

Structural and biochemical characterization of the essential DsbA-like disulfide bond forming protein from Mycobacterium tuberculosis. Chim, Nicholas; Harmston, Christine A.; Guzman, David J.; Goulding, Celia W. BMC Structural Biology. 2013, Vol. 13 Issue 1, p1-28. 28p. 6 Color Photographs, 1 Diagram, 3 Charts, 1 Graph. http://dx.doi.org/10.1186/1472-6807-13-23.

Structural snapshot of cyclic nucleotide binding domains from cyclic nucleotide-sensitive ion channels. Schünke, Sven; Stoldt, Matthias. Biological Chemistry. Nov2013, Vol. 394 Issue 11, p1439-1451. 13p. http://dx.doi.org/10.1515/hsz-2013-0228.

Metal-mediated crystallization of the xylose transporter XylE from Escherichia coli in three different crystal forms. Quistgaard, Esben M.; Löw, Christian; Moberg, Per; Nordlund, Pär. Journal of Structural Biology. Nov2013, Vol. 184 Issue 2, p375-378. 4p. http://dx.doi.org/10.1016/j.jsb.2013.09.009.

Fundamental studies for the proton polarization technique in neutron protein crystallography. Tanaka, Ichiro; Kusaka, Katsuhiro; Chatake, Toshiyuki; Niimura, Nobuo. Journal of Synchrotron Radiation. Nov2013, Vol. 20 Issue 6, p958-961. 4p. http://dx.doi.org/10.1107/S0909049513020815.

Strategies for crystallizing a chromatin protein in complex with the nucleosome core particle.  Makde, Ravindra D.; Tan, Song. Analytical Biochemistry. Nov2013, Vol. 442 Issue 2, p138-145. 8p. http://dx.doi.org/10.1016/j.ab.2013.07.038.

The Structure of the Cytochrome P450cam-Putidaredoxin Complex Determined by Paramagnetic NMR Spectroscopy and Crystallography. Hiruma, Yoshitaka; Hass, Mathias A.S.; Kikui, Yuki; Liu, Wei-Min; Ölmez, Betül; Skinner, Simon P.; Blok, Anneloes; Kloosterman, Alexander; Koteishi, Hiroyasu; LÖhr, Frank; Schwalbe, Harald; Nojiri, Masaki; Ubbink, Marcellus. Journal of Molecular Biology. Nov2013, Vol. 425 Issue 22, p4353-4365. 13p. http://dx.doi.org/10.1016/j.jmb.2013.07.006.

Phaser.MRage: automated molecular replacement. Bunkóczi, Gábor; Echols, Nathaniel; McCoy, Airlie J.; Oeffner, Robert D.; Adams, Paul D.; Read, Randy J. Acta Crystallographica: Section D. Nov2013, Vol. 69 Issue 11, p2276-2286. 11p. http://dx.doi.org/10.1107/S0907444913022750.

The structure and regulation of magnesium selective ion channels. Payandeh, Jian; Pfoh, Roland; Pai, Emil F. BBA - Biomembranes. Nov2013, Vol. 1828 Issue 11, p2778-2792. 15p. http://dx.doi.org/10.1016/j.bbamem.2013.08.002.

Advances in Rosetta structure prediction for difficult molecular-replacement problems. DiMaio, Frank. Acta Crystallographica: Section D. Nov2013, Vol. 69 Issue 11, p2202-2208. 7p. http://dx.doi.org/10.1107/S0907444913023305.

Buried Glory: Portraits of Soviet Scientists
     by Istvan Hargittai
     Oxford University Press, 2013 ISBN 978-0-19-998559

Dr. Istvan Hargittai's book, Buried Glory, describes the lives, scientific work, and personalities of fourteen brilliant male scientists from the former Soviet Union. Seven of them were Nobel laureates who made crucial discoveries in the fields of physics and chemistry. Many at certain times in their lives were also victims of terror or persecution because of their Jewish heritage or their support for ideas that ran counter to Joseph Stalin or the Communist Party's paranoid and isolationist agenda. More than half are buried in the Novodevichy Cemetery in Moscow, Russia. The author personally interviewed some of his subjects and did extensive research, with many annotations for each chapter.

The author did an insightful analysis of the wrenching conflicts between many of the subjects' love of country and their deep dismay at some of the actions of their political leaders and their ideology. Some of the scientists described were involved in the development of Soviet nuclear weapons. As such, they had the same conflict between a desire to succeed and the recognition of the horror of the actual use of the weapons that Western scientists had at the end of World War II.

All of us have heard of Andrei Sakharov, but he was only one of many who suffered for dissidence. Each character is depicted as intensely human, with all the associated flaws, intrigue, and large egos that often go with immense intellectual prowess. Of course they experienced the same fun and wonder in the lab or in theoretical discovery as all of us do.

The experience of reading this book was difficult at first, because I found the writing to be a bit rambling and disconnected, but it was worth it because of what I learned. An example that appeals to crystallographers is Alexandr Kitaigorodskii, who predicted the distribution frequencies of the space groups based on favorable molecular close packing using wooden arbitrarily shaped molecule "models."

As a scientist I have always enjoyed the internationality of our webs of connections, and I have had many colleagues who grew up in the Soviet Union. The excitement of scientific discovery often seems to transcend our other more "tribal" memberships. Reading this book made me ask myself whether I would have spoken up or stayed silent at some of the atrocities that these scientists witnessed. The author also made a perceptive and ironic observation that the conditions that led to some of the great discoveries made by these scientists may not be present in the more materialistic Russia of today. One wonders if the same quality of scientific discovery that our Western countries had in the twentieth century will ever be replicated with ever-decreasing funding and budget crises.