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Crystallography
in the news
December 1, 2015. CRISPR/Cas9, a defense system that bacteria use to protect against invading genetic elements, was adapted by scientists in 2012 as a tool to edit genomes in the lab. Now, after directly watching individual Cas9 enzymes explore DNA inside living cells, Howard Hughes Medical Institute (HHMI) scientists report that they have a better understanding of how Cas9 speeds through this task, testing out potential targets but quickly moving on from those that are not an exact match.
December 3, 2015. New research has revealed how a potentially useful predatory bacterium called Bdellovibrio protects itself against its own weapons when it invades other bacteria. The study by the labs of Professor Liz Sockett and Dr Andrew Lovering at the Universities of Nottingham and Birmingham offers insights into early steps in the evolution of bacterial predators and will help to inform new ways to fight antimicrobial resistance.
December 7, 2015. In order to figure out the role of a key protein in HIV's life cycle, researchers at the Bond Life Sciences Center are exploring the protein's structure. Stefan Sarafianos, the lead author of the study, found a building block that formed the virus' capsid, a protein shell that encloses the genetic material of a virus.
December 10, 2015. Infinitesimal fluctuations occurring on the milli- and even nano-second time scales within the three-dimensional structure of enzymes may be one of the keys to explaining protein function. Professor Nicolas Doucet's team at INRS has demonstrated that even when certain amino acids are far from the active site of an enzyme, a change in their flexibility and atomic fluctuations can significantly impact enzyme activity.
December 10, 2015. The Periodic Table of Protein Complexes, created by an interdisciplinary team led by researchers at the Wellcome Genome Campus and the University of Cambridge, offers a new way of looking at the enormous variety of structures that proteins can build in nature. More importantly, it suggests which ones might be discovered next and how entirely novel structures could be engineered.
December 11, 2015. An enzyme crucial to the process of DNA repair in our cells has been mapped in atomic detail by researchers at the University of Dundee, the UK's top-rated University for Biological Sciences. In one such process, DNA temporarily forms interconnections, called junctions, that much be processed by special enzymes, including one called GEN1, which has now been mapped by the Dundee team.
December 11, 2015. A new study, led by scientists at The Scripps Research Institute (TSRI), shows how different pharmaceutical drugs hit either the "on" or "off" switch of a signaling protein linked to asthma, obesity and type 2 diabetes. Researchers focused on the beta-2 adrenergic receptor (β2AR), a protein that sits on the cell membrane, where it binds external molecules and sends signals to the inside of the cell.
December 11, 2015. Yeast FNIP1/2 orthologue Lst4 confirmed as DENN-family protein. Using X-ray crystallography, Pacitto et al. solved the structure of the N-terminal longin domain of yeast FNIP1/2 orthologue Lst4 (residues 58226) to 2.14 Å (PDB ID: 4ZY8). This showed the classic longin domain architecture of a core five-strand β-sheet with a single a-helix on the concave side and two α-helices on the convex side, identifying Lst4 as a DENN-family protein.
December 14, 2014. The BIOSTRUCT-X project is hosting a workshop on Ensemble Refinement of Protein Crystal Structures at the Institute of Chemical and Biological Technology (ITBQ) in Oeiras, Portugal between 31 January and 2 February 2016. During the first two days, the programme will consist of lectures in the mornings and tutorials and practical sessions in the afternoons.
Product spotlight: XtaLAB MM007-HF
The XtaLAB MM007-HF system includes a VariMax optic coupled to the MicroMax-007 HF, which provides the best balance between outstanding performance for a wide range of crystal types. As the most popular microfocus rotating anode X-ray source for structural biology, the Rigaku MicroMax-007 HF provides brilliance equaling the very best competitive products with a smaller focal spot and while providing lower cost-of-ownership and higher productivity. High uptimes and "designed-in" maintainability differentiate the MicroMax-007 HF from the competition. The MicroMax-007 HF rotating anode generator offers two ports and can be equipped with detector systems on each. Alternatively, one port can be configured for biological SAXS experiments.
For more about the XtaLAB MM007-HF.
Lab in the spotlight
Alex Wlodawer, Ph.D.
Senior Investigator
Head, Protein Structure Section
Center for Cancer Research
National Cancer Institute, Frederick, MD
The Protein Structure Section investigates the relationship between protein structure and function, mainly by the technique of high-resolution X-ray diffraction. Some of the areas of interest are directly involved in elucidating structural features of the molecules that could explain their importance to understanding cancer and AIDS, but they are also active in the development of methods for protein crystallography.
Crystallographic studies of proteases have been an important area of research of this Section since its establishment. They have been particularly active in the investigation of structure-function relationship in aspartic proteases, including clinically important retroviral enzymes. They have investigated structure-function relationship in retroviral proteases from several sources, such as HIV-1, FIV, RSV, EIAV, HTLV-1, and XMRV. They are also investigating the bacterial ATP-dependent protease Lon, having found that its proteolytic domain has a unique fold and thus establishes a new family of proteases with a Ser-Lys catalytic dyad.
Other areas of interest include cytokines and cytokine receptors and lectins with antiviral activity.
Useful link:
xia2
xia2 is an expert system to perform X-ray diffraction data processing on your behalf, using your software with little or no input from you. It will correctly handle multi-pass, multi-wavelength data sets but it is not a data processing package.
Developed by Graeme Winter, Tthis software is distributed under the BSD license for all users. Everyone who uses this software is invited to join the xia2bb mailing list.
Selected
recent crystallographic papers
Structural modeling of proteins by integrating small-angle x-ray scattering data. Zhang Yong-Hui; Peng Jun-Hui; Zhang Zhi-Yong. Chinese Physics B. Dec2015, Vol. 24 Issue 12, p1-1. 1p. DOI: 10.1088/1674-1056/24/12/126101.
New paradigms in GPCR drug discovery. Jacobson, Kenneth A. Biochemical Pharmacology. Dec2015, Vol. 98 Issue 4, p541-555. 15p. DOI: 10.1016/j.bcp.2015.08.085.
Unravelling the shape and structural assembly of the photosynthetic GAPDH-CP12-PRK complex from Arabidopsis thaliana by small-angle X-ray scattering analysis. Del Giudice, Alessandra; Pavel, Nicolae Viorel; Galantini, Luciano; Falini, Giuseppe; Trost, Paolo; Fermani, Simona; Sparla, Francesca. Acta Crystallographica: Section D. Dec2015, Vol. 71 Issue 12, p2372-2385. 14p. DOI: 10.1107/S1399004715018520.
High-resolution crystal structure of a hepatitis B virus replication inhibitor bound to the viral core protein. Klumpp, Klaus; Lam, Angela M.; Lukacs, Christine; Vogel, Robert; Ren, Suping; Espiritu, Christine; Baydo, Ruth; Atkins, Kateri; Abendroth, Jan; Liao, Guochun; Efimov, Andrey; Hartman, George; Flores, Osvaldo A. Proceedings of the National Academy of Sciences of the United States of America. 12/8/2015, Vol. 112 Issue 49, p15196-15201. 6p. DOI: 10.1073/pnas.1513803112.
Retrotransposition and Crystal Structure of an Alu RNP in the Ribosome-Stalling Conformation. Ahl, Valentina; Keller, Heiko; Schmidt, Steffen; Weichenrieder, Oliver. Molecular Cell. Dec2015, Vol. 60 Issue 5, p715-727. 13p. DOI: 10.1016/j.molcel.2015.10.003.
Structure-function relationships in Gan42B, an intracellular GH42 β-galactosidase from Geobacillus stearothermophilus. Solomon, Hodaya V.; Tabachnikov, Orly; Lansky, Shifra; Salama, Rachel; Feinberg, Hadar; Shoham, Yuval; Shoham, Gil. Acta Crystallographica: Section D. Dec2015, Vol. 71 Issue 12, p2433-2448. 16p. DOI: 10.1107/S1399004715018672.
Structure of the BoNT/A1 – receptor complex. Benoit, Roger M.; Frey, Daniel; Wieser, Mara M.; Thieltges, Katherine M.; Jaussi, Rolf; Capitani, Guido; Kammerer, Richard A. Toxicon. Dec2015 Part A, Vol. 107, p25-31. 7p. DOI: 10.1016/j.toxicon.2015.08.002.
Exploiting Transient Protein States for the Design of Small-Molecule Stabilizers of Mutant p53. Joerger, Andreas C.; Bauer, Matthias R.; Wilcken, Rainer; Baud, Matthias G.J.; Harbrecht, Hannes; Exner, Thomas E.; Boeckler, Frank M.; Spencer, John; Fersht, Alan R. Structure. Dec2015, Vol. 23 Issue 12, p2246-2255. 10p. DOI: 10.1016/j.str.2015.10.016.
Unexpected features and mechanism of heterodimer formation of a herpesvirus nuclear egress complex. Lye, Ming F.; Sharma, Mayuri; El Omari, Kamel; Filman, David J.; Schuermann, Jonathan P.; Hogle, James M.; Coen, Donald M. EMBO Journal. 12/2/2015, Vol. 34 Issue 23, p2937-2952. 16p. DOI: 10.15252/embj.201592651.
The molecular structure of the silk fibers from Hymenoptera aculeata (bees, wasps, ants). Fraser, R.D. Bruce; Parry, David A.D. Journal of Structural Biology. Dec2015, Vol. 192 Issue 3, p528-538. 11p. DOI: 10.1016/j.jsb.2015.10.017.
A crystal structure of 2-hydroxybiphenyl 3-monooxygenase with bound substrate provides insights into the enzymatic mechanism. Kanteev, Margarita; Bregman-Cohen, Almog; Deri, Batel; Shahar, Anat; Adir, Noam; Fishman, Ayelet. BBA - Proteins & Proteomics. Dec2015, Vol. 1854 Issue 12, p1906-1913. 8p. DOI: 10.1016/j.bbapap.2015.08.002.
Super-Resolution Microscopy: From Single Molecules to Supramolecular Assemblies. Sydor, Andrew M.; Czymmek, Kirk J.; Puchner, Elias M.; Mennella, Vito. Trends in Cell Biology. Dec2015, Vol. 25 Issue 12, p730-748. 19p. DOI: 10.1016/j.tcb.2015.10.004.
Structure of Zeste–DNA Complex Reveals a New Modality of DNA Recognition by Homeodomain-Like Proteins. Gao, Guan-Nan; Wang, Mingzhu; Yang, Na; Huang, Ying; Xu, Rui-Ming. Journal of Molecular Biology. Dec2015, Vol. 427 Issue 24, p3824-3833. 10p. DOI: 10.1016/j.jmb.2015.10.008.
Structure of product-bound SMG1 lipase: active site gating implications. Shaohua Guo; Jinxin Xu; Pavlidis, Ioannis V.; Dongming Lan; Bornscheuer, Uwe T.; Jinsong Liu; Yonghua Wang. FEBS Journal. Dec2015, Vol. 282 Issue 23, p4538-4547. 10p. DOI: 10.1111/febs.13513.
Expression, Crystallization and Preliminary X-ray Diffraction Analyses of Med-ORF10 in the Biosynthetic Pathway of an Antitumor Antibiotic Medermycin. Liu, Yanli; Liu, Shasha; Yang, Tingting; Guo, Xiaoxia; Jiang, Yali; Zahid, Kashif; Liu, Ke; Liu, Jinlin; Yang, Jihong; Zhao, Haobin; Yang, Yi; Li, Aiying; Qi, Chao. Protein Journal. Dec2015, Vol. 34 Issue 6, p404-410. 7p. DOI: 10.1007/s10930-015-9635-9.
Protein Kinase A Catalytic Subunit Primed for Action: Time-Lapse Crystallography of Michaelis Complex Formation. Das, Amit; Gerlits, Oksana; Parks, Jerry M.; Langan, Paul; Kovalevsky, Andrey; Heller, William T. Structure. Dec2015, Vol. 23 Issue 12, p2331-2340. 10p. DOI: 10.1016/j.str.2015.10.005.
Small-angle scattering determination of the shape and localization of human cytochrome P450 embedded in a phospholipid nanodisc environment. Skar-Gislinge, Nicholas; Kynde, Søren A. R.; Denisov, Ilia G.; Ye, Xin; Lenov, Ivan; Sligar, Stephen G.; Arleth, Lise. Acta Crystallographica: Section D. Dec2015, Vol. 71 Issue 12, p2412-2421. 10p. DOI: 10.1107/S1399004715018702.
Structural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking. Froese, D. Sean; Kopec, Jolanta; Fitzpatrick, Fiona; Schuller, Marion; McCorvie, Thomas J.; Chalk, Rod; Plessl, Tanja; Fettelschoss, Victoria; Fowler, Brian; Baumgartner, Matthias R.; Yue, Wyatt W. Journal of Biological Chemistry. 12/4/2015, Vol. 290 Issue 49, p29167-29177. 11p. DOI: 10.1074/jbc.M115.683268.
Conformational Transitions that Enable Histidine Kinase Autophosphorylation and Receptor Array Integration. Greenswag, Anna R.; Muok, Alise; Li, Xiaoxiao; Crane, Brian R. Journal of Molecular Biology. Dec2015, Vol. 427 Issue 24, p3890-3907. 18p. DOI: 10.1016/j.jmb.2015.10.015.
Book review:
Computed Tomography: Principles, Design, Artifacts and Recent Advances, Third Edition
By Jiang Hsieh, SPIE Press, Bellingham, WA, 2015, 666 pages, ISB13: 978-1628418255.
You might wonder why I chose this book for the December review. In October, I received a list of new publications from the Society of Photo-Optical Instrumentation Engineers (SPIE) at about the same time as the nano3DX and CTLab systems were installed in the applications lab here in The Woodlands. Since I have not found a satisfactory text on X-ray microcomputed tomography, I thought this book might be a good substitute, since many of the principles associated with medical CT are the same.
The author is the Chief Scientist at GE Healthcare, so there a slight bias toward GE solutions, but where appropriate other solutions are described. As shown in the title, this is the third edition. I checked the first edition at Amazon and saw that it had only 338 pages. At 666 pages, one can see that a lot of material has been added since 2003. The book is laid out as a text book, with problems at the end of each chapter. It is very well referenced, up to and including 2015.
The book starts with an introduction to conventional tomography, then describes computed tomography and its history. The former method builds the volume of interest by blurring all but one plane. Multiple planes are imaged and an overall volume is generated – not a very low dose method.
The second chapter is devoted to the mathematical and physical principles that are necessary to understanding image collection, processing and reconstruction. A few pages cover the topic of the sinogram, a reordering of the projection data to detect errors or anomalies for further processing. The next chapter covers the reconstruction of an object from projection data: the Fourier slice method, filtered back projection, fan-beam reconstruction and iterative reconstruction. Chapter 4 covers the display of the reconstructed volume, including such modern methods as 3D printing.
The next two chapters cover instrumentation, first looking at performance issues and then the components of CT scanners.
I found chapter 7 to be particularly enlightening, as it provides a clear description of a number of artifacts that can arise during the CT experiment and how to resolve them, either by the correct experimental setup or by specialized algorithms. Here one has to keep in mind that medical CT generally has two or perhaps three major components, soft tissue, bone and occasionally a piece of metal. The types of samples measured in non-medical applications have a much broader range of densities, so the algorithms described will not be as effective. Chapter 8 describes the use of computer simulations to understand system performance.
Chapters 9 and 10 cover helical scan CT, multislice CT and cone-beam CT. The advantages and disadvantages of these methods are considered, as are the changes in the measurement relative to simpler CT methods. Chapter 11 covers dose reduction methods. Chapter 12 describes a number of specialized CT techniques, including gating imaging and dual energy CT.
Someone new to material science would be well served by this text since it provides clear explanations and solutions to problems that will be encountered in analyzing a variety of samples.
Joseph D. Ferrara, Ph.D.
Chief Science Officer
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