Crystallography in the news

July 2, 2014. Certain bacteria found around coca plants have previously been found to contain an enzyme, Cocaine Esterase, that breaks down cocaine. Researchers at the University of Kentucky, led by Prof. Chang-Guo Zhan, have employed X-ray crystallography to reach a breakthrough necessary to apply the enzyme to human cocaine addiction.

July 4, 2014. Changyong Song and colleagues from the RIKEN SPring-8 Center and RIKEN Advanced Institute for Computational Science have devised a structural analysis scheme based on complementary advanced X-ray techniques that has allowed them to peer inside an RNA macromolecular complex for the first time. The technique combines single-shot free-electron laser diffraction with synchrotron coherent X-ray imaging. This X-ray structural analysis scheme is nondestructive, providing deeper penetration into target materials and enhanced resolution limited only by the wavelength of X-rays used. The scheme is also highly versatile because, unlike many other analysis schemes, no prior information about the sample is required to complete the structural analysis.

July 8, 2014. An international team from CIC bioGUNE, the University of Liverpool and the US research centre USC-UCLA has successfully unraveled the mechanism by which two proteins, MATα2 and MATβ, bind to each other, thereby promoting the reproduction of tumour cells in liver and colon cancers. As a result of this discovery, it is now known which part of their respective structures can be blocked to prevent these proteins from joining together. This is very important as when these proteins bind to each other, the production of a molecule known as SAMe, which plays a role in uncontrolled tumour cell growth, increases considerably.

July 10, 2014. The Spanish National Cancer Research Center (CNIO) Macromolecular Crystallography Group has managed to reprogram the binding of a protein called BurrH in order to redirect it towards specific DNA regions. BurrH contains a DNA-binding domain (BuD) with a central region composed of 19 repeats of a helix-loop-helix modular domain. Guillermo Montoya, the researcher who led the study, says the discovery "will allow us to modify and edit the instructions contained in the genome to treat genetic diseases or to develop genetically-modified organisms."

July 10, 2014. Professors Peter Moody and Emma Raven from the University of Leicester worked with Dr Matthew Blakeley, Dr Susana Teixeira and Cecilia Casadei from the Institut Laue-Langevin, along with scientists from the Maier-Leibnitz Zentrum (MLZ) and the University of Manchester, to solve the mystery of the ferryl heme Compound I structure using neutron crystallography. The ferryl heme in Compound I is not protonated but, unexpectedly, the results showed that one of the amino acid side chains (a histidine) on the molecule is doubly protonated, which raises questions of its own in terms of mechanisms for oxygen activation in heme enzymes.

July 14, 2014. Serial Femtosecond Crystallography (SFX) is an international consortium of scientists working to deliver a protein crystallography facility that will enable researchers to better analyse the structure of many biomolecules. This new facility is currently under construction at the European X-ray Free Electron Laser (XFEL) in Hamburg, Germany.

July 15, 2014. Saint Louis University scientists have discovered that removal of disordered sections of a protein's structure reveals the molecular mechanism of a key reaction that initiates blood clotting. Enrico Di Cera, M.D., chair of the Edward A. Doisy department of biochemistry and molecular biology at Saint Louis University, studies thrombin, a key vitamin K-dependent blood-clotting protein, and its inactive precursor prothrombin (or coagulation factor II).

July 18, 2014. Hideo Ago and colleagues from the RIKEN SPring-8 Center, along with researchers from other institutions in Japan, have now developed an X-ray technique that allows one of the most powerful modern X-ray machines, the X-ray free electron laser (XFEL) at the SPring-8 synchrotron facility, to be used to study large, complex molecules without radiation damage. To avoid damage from successive pulses hitting the same spot in the crystal, the X-ray spot size is made very small and successive measurements are taken at different locations in the crystal. Averaging the X-ray patterns obtained from various locations then allows the optimized crystal structure to be determined.

July 20, 2014. Rice theoretical biologist Peter Wolynes and his team at the university's Center for Theoretical Biological Physics (CTBP) have applied his energy landscape theory to membrane proteins. Wolynes and his colleagues used raw genomic information to predict how strands of amino acids will fold into functional proteins by following paths of least resistance (aka, the principle of minimal frustration) dictated by the energy associated with each "bead" in the strand. Scientists now have an algorithm to predict membrane protein structure based on the raw genome sequence.

July 22, 2014. Scientists at the Max Planck Institute for Developmental Biology in Tubingen have discovered that proteins can be constructed of similar amino acid chains even when their three-dimensional shapes differ significantly. This suggests that the proteins that exist today arose from common precursors. Presumably, in the course of evolution they were built up from smaller fragments according to a modular principle.

Product spotlight: BioSAXS ASC

The new BioSAXS ASC provides support for samples supplied in either 96-well PCR plates or 0.2 mL PCR tube arrays

Rigaku recently introduced the BioSAXS-2000, which features the new OptiSAXS optic that provides better than 2-fold higher flux and, thus, shorter exposure times for macromolecular samples. Because data collection is faster with the BioSAXS-2000, automated tools for sample mounting, data collection and data analysis become especially important. To address the higher throughput needs offered by the BioSAXS-2000, Rigaku now offers a high capacity Automatic Sample Change (ASC) for those labs that desire unattended sample mounting and data collection.

The BioSAXS ASC provides support for samples supplied in either 96-well PCR plates or 0.2 mL PCR tube arrays and seamlessly automates sample loading, data collection and flow cell washes between samples. The BioSAXS ASC system includes an intuitive user interface for setting up samples as well as sample temperature control, support for foil sealed sample trays/tubes and customizable protocols for cleaning the flow cell. For those labs that also desire automated SAXS data analysis, Rigaku offers the Automatic Analysis Pipeline (AAP) that provides instantaneous processing and calculation of important structural parameters using the popular ATSAS package. When combined, the BioSAXS ASC and AAP provide reliable SAXS data collection and analysis so that you can focus more time where it counts - publication of results.

Ask for more information.

Joshua Sakon, Ph.D.
Associate Professor
Department of Chemistry and Biochemistry
University of Arkansas

Josh's NIH research at the University of Arkansas has resulted in some very interesting results showing that bone and skin growth and repair can be promoted.

To understand the mystery of biological processes in terms of chemistry and physics, three-dimensional structural information at near atomic resolution is desired. The Sakon lab uses the X-ray diffraction method to explore the events in medicinally important biochemistry at an atomic level. Their ultimate goal is to bring drugs/devices from bench to bedside. One of the drug candidates, PTH-CBD, is licensed to BiologicsMD. Other drug candidates are being helped by others.

Sakon Group (left); X-ray Crystal Structure of Collagenase CBD with (B) and without (A) Calcium (right).

The Prezi Top 100 online resources will help you give the best presentations of your life. They have scoured the web looking for the most inspirational and useful resources for anyone looking to improve their presentation skills; the #PreziTop100 is the result of all this hard work. The assembled this list by looking at both popularity data (Alexa, Google pagerank, pageviews, Klout score, social media followers, and social engagement) and the quality of the content as determined by a panel of Prezi judges. Here are the best videos, articles, presentations, and blogs to get your creative juices flowing.

Scoring docking conformations using predicted protein interfaces. Esmaielbeiki, Reyhaneh; Nebel, Jean-Christophe. BMC Bioinformatics. 2014, Vol. 15 Issue 1, p1-34. 34p. 1 Color Photograph, 4 Diagrams, 9 Charts, 3 Graphs. DOI: 10.1186/1471-2105-15-171.

Automated identification of crystallographic ligands using sparse-density representations. Carolan, C. G.; Lamzin, V. S. Acta Crystallographica: Section D. Jul2014, Vol. 70 Issue 7, p1844-1853. 10p. DOI: 10.1107/S1399004714008578.

Single-step antibody-based affinity cryo-electron microscopy for imaging and structural analysis of macromolecular assemblies. Yu, Guimei; Vago, Frank; Zhang, Dongsheng; Snyder, Jonathan E.; Yan, Rui; Zhang, Ci; Benjamin, Christopher; Jiang, Xi; Kuhn, Richard J.; Serwer, Philip; Thompson, David H.; Jiang, Wen. Journal of Structural Biology. Jul2014, Vol. 187 Issue 1, p1-9. 9p. 
DOI: 10.1016/j.jsb.2014.04.006.

M-free: Scoring the reference bias in sub-tomogram averaging and template matching. Yu, Zhou; Frangakis, Achilleas S. Journal of Structural Biology. Jul2014, Vol. 187 Issue 1, p10-19. 10p. DOI: 10.1016/j.jsb.2014.05.007.

Ligand discovery: Docking points. Barril, Xavier. Nature Chemistry. Jul2014, Vol. 6 Issue 7, p560-561. 2p. DOI: 10.1038/nchem.1986.

Use of Cross-Linked Poly(ethyleneglycol)-Based Hydrogelsfor Protein Crystallization. Gavira, Jose A.; Cera-Manjarres, Andry; Ortiz, Katia; Mendez, Janet; Jimenez-Torres, Jose A.; Patiño-Lopez, Luis D.; Torres-Lugo, Madeline. Crystal Growth & Design. Jul2014, Vol. 14 Issue 7, p3239-3248. 10p. DOI: 10.1021/cg401668z.

Structure determination by X-ray crystallography: analysis by X-rays and neutrons. Gruene, Tim. Crystallography Reviews. Jul-Sep2014, Vol. 20 Issue 3, p235-236. 2p. DOI: 10.1080/0889311X.2014.885510.

Growth of Diffraction-Quality Protein Crystals Usinga Harvestable Microfluidic Device. Lee, Michael J. Y.; Faucher, Frédérick; Jia, Zongchao. Crystal Growth & Design. Jul2014, Vol. 14 Issue 7, p3179-3181. 3p. DOI: 10.1021/cg500450b.

Crystallization screening: the influence of history on current practice. Luft, Joseph R.; Newman, Janet; Snell, Edward H. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p835-853. 19p. DOI: 10.1107/S2053230X1401262X.

Cloning, purification, crystallization and preliminary X-ray studies of the putative type VI secretion immunity protein Tli5 (PA5088) from Pseudomonas aeruginosa. Chen, Zhen; Gao, Zengqiang; Hu, Haidai; Xu, Jianhua; Zhang, Heng; Dong, Yuhui. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p903-905. 3p. 
DOI: 10.1107/S2053230X14010164.

Crystallization and preliminary analysis of the NqrA and NqrC subunits of the Na+-translocating NADH:ubiquinone oxidoreductase from Vibrio cholerae. Vohl, Georg; Nedielkov, Ruslan; Claussen, Björn; Casutt, Marco S.; Vorburger, Thomas; Diederichs, Kay; Möller, Heiko M.; Steuber, Julia; Fritz, Günter. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p987-992. 6p. DOI: 10.1107/S2053230X14009881.

Purification, crystallization and preliminary X-ray crystallographic analysis of the UDP- N-acetylmuramoyl-tripeptide-D-alanyl-D-alanine ligase (MurF) from Acinetobacter baumannii. An, Young Jun; Jeong, Chang-Sook; Yu, Jeong Hee; Chung, Kyung Min; Cha, Sun-Shin. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p976-978. 3p. 
DOI: 10.1107/S2053230X14009984.

Preliminary X-ray crystallographic analysis of an engineered glutamyl-tRNA synthetase from Escherichia coli. Chongdar, Nipa; Dasgupta, Saumya; Datta, Ajit Bikram; Basu, Gautam. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p922-927. 6p. 
DOI: 10.1107/S2053230X14010723.

Purification, crystallization and preliminary X-ray analysis of a putative nucleotide phosphohydrolase, YpgQ, from Bacillus subtilis. Jeon, Ye Ji; Song, Wan Seok; Yoon, Sung-il. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p984-986. 3p. 
DOI: 10.1107/S2053230X14006682.

Crystallization and preliminary crystallographic studies of the complement 1qA globular domain from zebrafish, Dare-C1qAgD. Yuan, Hongyu; Chen, Rong; Liu, Yanjie; Tariq, Mansoor; Sun, Yaping; Xia, Chun. Acta Crystallographica: Section F, Structural Biology Communications. Jul2014, Vol. 70 Issue 7, p911-914. 4p. 
DOI: 10.1107/S2053230X14010747.

Book review: Proof: The Science of Booze

     by Adam Rogers
     Houghton Mifflin Harcourt Publishing, New York, 272 pp, ISBN: 978-0547897967.

Adam Rogers' recent work, Proof: The Science of Booze, is exactly as its subject matter would suggest: fun. Rogers' own passion for a good brew comes through quite vividly, and motivates the text quite nicely.

He attempts to trace the "life" of alcohol, from its "conception" via fermentation to its "haunting" of the human body via the infamous hangover. Rogers also touches on the history of alcohol as a beverage fit for human consumption.

Rogers' claim that there is not a substantial scientific explanation for the hangover (and likewise, there is no "cure-all") intrigues me. As I have been required to read The Odyssey multiple times for academic purposes (as well as having read it once as a child for pleasure), I found it particularly entertaining-and perhaps a bit disconcerting-that a hangover severe enough to result in psychiatric dissociation is called Elpenor syndrome. Its namesake was a sailor companion of Odysseus in Homer's epic who got drunk and fell asleep on the roof of Circe's castle, only to fall off and die when he woke.

I had always been told, and believed, that hangovers were caused by dehydration, and that the best prevention and cure was simple hydration. Rogers does not deny that drinking alcohol dehydrates you, but he claims that this dehydration does not solely account for the painful reality of the morning after.

Rogers also debunks the myth that vodka does not cause hangovers, as well as the myth that more drinking (i.e. Bloody Marys) are an effective cure. Studies have shown that people who drink enough vodka to raise their blood alcohol content (BAC) to between 0.1 and 0.15 get hangovers, as do people who drink enough of almost any other kind of alcohol. Morning cocktails may temporarily delay the crippling effects of a hangover, but the hangover is inevitable.

Rogers quite entertainingly details the results of his own self-proclaimed hangover experiment, where he and two of his friends decided to get very drunk (BAC over 0.1) and test the effectiveness of various hangover "cures." However, their breathalyzer was broken, so in order to ensure that they would have a hangover, they overcompensated and drank quite a bit. Rogers believes that they went so over the limit of 0.1 that anything they tried the next morning proved ineffective. Although Rogers admits the "experiment" was hardly scientific, it is a nice anecdote upon which to end his book.

All in all, Rogers' Proof is a fun read, light enough for summer but also substantial enough to make it worthwhile.