Monthly message

This week we celebrate the 65th annual meeting of the American Crystallographic Association. As a sponsor, we heartily thank all who traveled to Philadelphia in support of this most important event. Special congratulations are in order to the 2015 award winners: the B. E. Warren Award to Laurence Marks, Professor of Materials Science and Engineering at Northwestern University; the Martin J. Buerger Award to Greg Petsko, Mahon Professor of Neurology and Neuroscience at Weill Cornell Medical College and Tauber Professor of Biochemistry and Chemistry, Emeritus, at Brandeis University; and the Margaret Etter Early Career Award to Yan Jessie Zhang, Assistant Professor, Department of Chemistry and Biochemistry at the University of Texas at Austin. Enjoy the eNewsletter.

R.C. Tisdale Ph.D. – Editor

Crystallography in the news

July 1, 2015. Cocrystal Pharma Inc (OTCBB:COCP) continues to trade big volume over $1, maintaining itself among the volume leaders on the big boards. The stock recently made a big move up off its $0.25 base to highs over $1.50 a share. All the excitement on COCP is about billionaire Dr. Phillip Frost 100 million shares stake in the Company.

July 2, 2015. Stefan Sarafianos, an associate professor of molecular microbiology and immunology and the Chancellor's Chair of Excellence in molecular virology in the University of Missouri School of Medicine, and his team captured long sought detailed images of the HIV capsid protein in its natural state. The molecular model surprisingly revealed "ordered" water molecules at areas between the viral proteins.

July 3, 2015. A research group at Umeå University in Sweden has managed to capture and describe a protein structure that, until now, has been impossible to study. The discovery lays the base for developing designed enzymes as catalysts to new chemical reactions for instance in biotechnological applications.

July 9, 2015. European researchers have observed protein crystal growth in living cells in real time, gathering important information about in vivo crystal formation. They used two different proteins: firefly luciferase and a truncated version of an avian reovirus protein, called muNS, fused to GFP, which allowed them to monitor by fluorescence the initial steps of crystal formation in cells.

July 13, 2015. Ever since the discovery of DNA and RNA, scientists have wondered if we can manipulate or even create synthetic proxies for these molecules. Now it seems that artificial genetic material can be reliably created that not only interacts like its natural similes, but can even be "read" by cells.

July 15, 2015. Christopher Colbert, NDSU assistant professor of biochemistry at North Dakota State University, Fargo, has received a $348,000 grant from the National Institute of General Medical Sciences of the National Institutes of Health to conduct research on structure-function relationships of iron transport and transcriptional regulation in Gram-negative bacteria.

July 16, 2015. The structure of two parts of the Oskar protein, known to be essential for the development of reproductive cells, has been solved by scientists from EMBL Heidelberg. This advance has also enabled the team to gather the first insights into how this poorly understood protein functions.

July 27, 2015. At the American Crystallographic Association (ACA) 2015 meeting in Philadelphia, researchers from the National Cancer Institute presented three newly determined crystal structures, which collectively provide a starting point for structure-based drug design efforts to combat MERS. The work was presented by George Lountos, a scientist in the lab of primary investigator David Waugh.

Product spotlight: Xcalibur and Gemini

Xcalibur and Gemini single-crystal X-ray diffractometers from the Rigaku Oxford Diffraction division have a proven track record earned over many years. From the first Xcalibur installed in 1999 to the world's first co-mounted dual-source diffractometer, the Gemini (2005), both instruments have well-deserved reputations for providing great data quality, with outstanding system reliability. Xcalibur and Gemini systems employ Enhance fine-focus X-ray sources, which can be either molybdenum or copper radiation and are factory pre-aligned to give maximum intensity. Coupled with the either the highly sensitive and dynamic Eos, Atlas or CCD S2 detectors, these systems offer great data quality to meet the ever-increasing demands of the modern day laboratory environment.

Visit Rigaku.com for more information about the Xcalibur and Gemini.

Lab spotlight: Prof Paul Raithby

Professor Paul Raithby
Chair of Inorganic Chemistry
University of Bath

Paul Raithby has held the Chair of Inorganic Chemistry at the University of Bath since 2000. He is currently an EPSRC Senior Research Fellow (2006-2011) working on the development of time resolved crystallography. In his research he uses synchrotron radiation as one of his key research tools and has worked extensively at the Synchrotron Radiation Source, Daresbury Laboratory, and at the ESRF, Grenoble. He was chair of the working party that is developing the new "small molecule" single-crystal X-ray diffraction beamline (I19) that has been built at the Diamond synchrotron at the Rutherford Appleton Laboratory, Didcot. He is the immediate past President of the British Crystallographic Association (2006-2009) and is currently a member of the EPSRC Technical Opportunities Panel (TOP). He is also the Champion of the EPSRC Grand Challenge entitled "Directed Assembly of Extended Structures with Targeted Properties".

Paul Raithby's research interests are in the area of solid state materials and materials science, where he uses a range of synthetic, spectroscopic, diffraction and knowledge mining techniques to probe the correlation between materials and their properties. He is currently working on the development of new organometallic oligomers and polymers that have applications in the opto-electronics industry and on coordination complexes that can act as sensors and data storage materials.

Useful link: CCharPPI

Computational Characterisation of Protein-Protein Interactions

CCharPPI web server: computational characterization of protein–protein interactions from structure. As tools for calculating protein–protein interactions are scattered across a multitude of stand-alone programs, CCharPPI integrates many of these tools into a single web server. It calculates up to 108 parameters, including models of electrostatics, desolvation and hydrogen bonding, as well as interface packing and complementarity scores, empirical potentials at various resolutions, docking potentials and composite scoring functions.

Conformational plasticity of a native retroviral capsid revealed by x-ray crystallography. Obal, G.; Trajtenberg, F.; Carrión, F.; Tomé, L.; Larrieux, N.; Zhang, X.; Pritsch, O.; Buschiazzo, A. Science. 7/3/2015, Vol. 349 Issue 6243, p95-98. 4p. DOI: 10.1126/science.aaa5182.

Structure of Dimeric and Tetrameric Complexes of the BAR Domain Protein PICK1 Determined by Small-Angle X-Ray Scattering. Karlsen, Morten L.; Thorsen, Thor S.; Johner, Niklaus; Ammendrup-Johnsen, Ina; Erlendsson, Simon; Tian, Xinsheng; Simonsen, Jens B.; Høiberg-Nielsen, Rasmus; Christensen, Nikolaj M.; Khelashvili, George; Streicher, Werner; Teilum, Kaare; Vestergaard, Bente; Weinstein, Harel; Gether, Ulrik; Arleth, Lise; Madsen, Kenneth L. Structure. Jul2015, Vol. 23 Issue 7, p1258-1270. 13p. DOI: 10.1016/j.str.2015.04.020.

Structure versus function — The impact of computational methods on the discovery of specific GPCR–ligands. Bermudez, Marcel; Wolber, Gerhard. Bioorganic & Medicinal Chemistry. Jul2015, Vol. 23 Issue 14, p3907-3912. 6p. DOI: 10.1016/j.bmc.2015.03.026.

Protein secondary-structure description with a coarse-grained model. Kneller, Gerald R.; Hinsen, Konrad. Acta Crystallographica: Section D. Jul2015, Vol. 71 Issue 7, p1411-1422. 12p. DOI: 10.1107/S1399004715007191.

Protein-complex structure completion using IPCAS (Iterative Protein Crystal structure Automatic Solution). Zhang, Weizhe; Zhang, Hongmin; Zhang, Tao; Fan, Haifu; Hao, Quan. Acta Crystallographica: Section D. Jul2015, Vol. 71 Issue 7, p1487-1492. 6p. DOI: 10.1107/S1399004715008597.

Large conformational fluctuations of the multi-domain xylanase Z of Clostridium thermocellum. Rózycki, Bartosz; Cieplak, Marek; Czjzek, Mirjam. Journal of Structural Biology. Jul2015, Vol. 191 Issue 1, p68-75. 8p. DOI: 10.1016/j.jsb.2015.05.004.

Automated determination of fibrillar structures by simultaneous model building and fiber diffraction refinement. Potrzebowski, Wojciech; André, Ingemar. Nature Methods. Jul2015, Vol. 12 Issue 7, p679-684. 6p. DOI: 10.1038/nmeth.3399.

Selective GPCR ligands. Gmeiner, Peter. Bioorganic & Medicinal Chemistry. Jul2015, Vol. 23 Issue 14, p3879-3879. 1p. DOI: 10.1016/j.bmc.2015.03.030.

Ligand-Induced Proton Transfer and Low-Barrier Hydrogen Bond Revealed by X-ray Crystallography. Nichols, Derek A.; Hargis, Jacqueline C.; Sanishvili, Ruslan; Jaishankar, Priyadarshini; Defrees, Kyle; Smith, Emmanuel W.; Wang, Kenneth K.; Prat, Fabio; Renslo, Adam R.; Woodcock, H. Lee; Yu Chen. Journal of the American Chemical Society. 7/1/2015, Vol. 137 Issue 25, p8086-8095. 10p. DOI: 10.1021/jacs.5b00749.

Iterative projection algorithms in protein crystallography. II. Application. Lo, Victor L.; Kingston, Richard L.; Millane, Rick P. Acta Crystallographica. Section A, Foundations & Advances. Jul2015, Vol. 71 Issue 4, p451-459. 9p. DOI: 10.1107/S2053273315005574.

From bacterial to human dihydrouridine synthase: automated structure determination. Whelan, Fiona; Jenkins, Huw T.; Griffiths, Samuel C.; Byrne, Robert T.; Dodson, Eleanor J.; Antson, Alfred A. Acta Crystallographica: Section D. Jul2015, Vol. 71 Issue 7, p1564-1571. 8p. DOI: 10.1107/S1399004715009220.

A highly selective fluorescent sensor for zinc ion based on quinoline platform with potential applications for cell imaging studies. Pradhan, Ankur Bikash; Mandal, Sushil Kumar; Banerjee, Saikat; Mukherjee, Abhishek; Das, Suman; Khuda Bukhsh, Anisur Rahman; Saha, Amrita. Polyhedron. Jul2015, Vol. 94, p75-82. 8p. DOI: 10.1016/j.poly.2015.04.005.

Synthesis, Crystal Structure and Electrical Studies of Naphthoyl-Thiourea as Potential Organic Light Emitting Diode. Jasman, Siti; Khairul, Wan; Tagg, Tei; KuBulat, K.; Rahamathullah, Rafizah; Arshad, Suhana; Razak, Ibrahim; Tahir, Mohamed. Journal of Chemical Crystallography. Jul2015, Vol. 45 Issue 7, p338-349. 12p. DOI: 10.1007/s10870-015-0599-6.

A tethered niacin-derived pincer complex with a nickel-carbon bond in lactate racemase. Desguin, Benoît; Tuo Zhang; Soumillion, Patrice; Hols, Pascal; Jian Hu; Hausinger, Robert P. Science. 7/3/2015, Vol. 349 Issue 6243, p66-69. 4p. DOI: 10.1126/science.aab2272.

Discovery of a new chemical series of BRD4(1) inhibitors using protein-ligand docking and structure-guided design. Duffy, Bryan C.; Liu, Shuang; Martin, Gregory S.; Wang, Ruifang; Hsia, Ming Min; Zhao, He; Guo, Cheng; Ellis, Michael; Quinn, John F.; Kharenko, Olesya A.; Norek, Karen; Gesner, Emily M.; Young, Peter R.; McLure, Kevin G.; Wagner, Gregory S.; Lakshminarasimhan, Damodharan; White, Andre; Suto, Robert K.; Hansen, Henrik C.; Kitchen, Douglas B. Bioorganic & Medicinal Chemistry Letters. Jul2015, Vol. 25 Issue 14, p2818-2823. 6p. DOI: 10.1016/j.bmcl.2015.04.107.

Crystal structures, spectroscopic, electrochemical, and antibacterial properties of a series of new copper(II) Schiff base complexes. Imani, Nasibeh; Behzad, Mahdi; Rudbari, Hadi Amiri; Bruno, Giuseppe; Samari Jahromi, Hamideh; Khaleghian, Ali. Journal of Coordination Chemistry. Jul2015, Vol. 68 Issue 13, p2296-2306. 11p. 4 Diagrams, 4 Charts, 1 Graph. DOI: 10.1080/00958972.2015.1051476.

Macyranones: Structure, Biosynthesis, and Binding Mode of an Unprecedented Epoxyketone that Targets the 20S Proteasome. Keller, Lena; Plaza, Alberto; Dubiella, Christian; Grail, J. Michael; Kaiser, Marcel; Müller, Rolf. Journal of the American Chemical Society. 7/1/2015, Vol. 137 Issue 25, p8121-8130. 10p. DOI: 10.1021/jacs.5b03833.

Lights and shadows in the challenge of binding acyclovir, a synthetic purine-like nucleoside with antiviral activity, at an apical–distal coordination site in copper(II)-polyamine chelates. Pérez-Toro, Inmaculada; Domínguez-Martín, Alicia; Choquesillo-Lazarte, Duane; Vílchez-Rodríguez, Esther; González-Pérez, Josefa María; Castiñeiras, Alfonso; Niclós-Gutiérrez, Juan. Journal of Inorganic Biochemistry. Jul2015, Vol. 148, p84-92. 9p. DOI: 10.1016/j.jinorgbio.2015.03.006.

HDAC8: a multifaceted target for therapeutic interventions. Chakrabarti, Alokta; Oehme, Ina; Witt, Olaf; Oliveira, Guilherme; Sippl, Wolfgang; Romier, Christophe; Pierce, Raymond J.; Jung, Manfred. Trends in Pharmacological Sciences. Jul2015, Vol. 36 Issue 7, p481-492. 12p. DOI: 10.1016/j.tips.2015.04.013.

In vitro effect of temperature on the conformational structure and collagen binding of SdrF, a Staphylococcus epidermidis adhesin. Poto, Antonella; Papi, Massimiliano; Trivedi, Sheetal; Maiorana, Alessandro; Gavazzo, Paola; Vassalli, Massimo; Lowy, Franklin; Spirito, Marco; Montanaro, Lucio; Imbriani, Marcello; Arciola, Carla; Visai, Livia. Applied Microbiology & Biotechnology. Jul2015, Vol. 99 Issue 13, p5593-5603. 11p. DOI: 10.1007/s00253-015-6456-x.

Book reviews:

This month I am doing a series of short reviews of what I've been reading for fun this summer. Next month I'll provide a review of Hammond's 4th edition of The Basics of Crystallography and Diffraction.

The Wright Brothers by David McCollough, Simon & Schuster; 2015, New York, 336 pages, ISBN-13: 978-1476728742.

McCullough has the ability to make history come alive and this book is a great example. It is the story of how the Wright Brothers went from bicycle makers to the inventors of powered flight. I always knew that the Wrights had to have a lot of intestinal fortitude to get off the ground, but I never knew how savvy they were about protecting their intellectual property and their business interests.

Seveneves by Neal Stephenson, William Morrow, 2015, New York, 880 pages, ISBN-13: 978-0062190376.

The book starts off with the moon splitting into seven chunks for no apparent reason. This sends mankind into a frenzy to do what it can to save itself. From the page count it is obviously a long book but worth the read, if you like good science fiction. You'll notice the title is a palindrome—there is a reason, but I won't spoil it for you.

Elon Musk, Ashlee Vance, HarperCollins, New York, 2014, 400 pages, ISBN-13: 978-0062301239.

Stan Ovshinsky, founder of Osmic and Energy Conversion Devices, when asked in an interview about his batteries, said in Who Killed the Electric Car?, "We are changing the world, not with guns and bullets, but with technology." As I read Elon Musk, those words came to mind and made me realize Musk is doing exactly what Ovshinsky started to do. Here you'll follow Musk's path from childhood in South Africa to Tesla and SpaceX. I love the line, "I want to die on Mars, just not on impact."

The Geek Atlas: 128 Places Where Science and Technology Come Alive, John Graham-Cumming, O'Reilly Media, Sebastapol, CA, 2009, 544 pages, ISBN-13: 978-0596523206.

This book came out in 2009 but I caught an interview with the author on SciFri and bought a new copy for my wife. However, I could not let it sit on the kitchen table without going through it. In addition to providing the 128 locations, a description of the significance of each location is given. They are spread all over the world, with about 1/3 in the US and another 1/3 in the UK. I bought the hardcopy for my wife but I will buy a Kindle version for myself for my travels. By the way, the closest locations to the Philly ACA meeting are the Princeton Institute for Advanced Studies and the Horn Antenna (used in the discovery of the cosmic microwave background by Penzias and Wilson) in Holmdell NJ.

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