Crystallography in the news

August 1, 2014. In research funded by the US National Science Foundation and the US Department of Energy, the team of Yulia Pushkar and postdoctoral researcher Lifen Yanin at Purdue University in West Lafayette, Indiana, working with international colleagues, has focused their attention on the unicellular marine cyanobacterium Thermosynechococcus elongatus with a view to understanding photosynthesis using serial femtosecond crystallography.

August 6, 2014. Saint Louis University investigators, led by Prof. Duane Grandgenett, report catching integrase, the part of retroviruses like HIV that is responsible for insertion of the viral DNA into human cell DNA, in the presence of a drug designed to thwart it. This achievement sets the stage to use X-ray crystallography to develop complete images of HIV that include integrase, which in turn will help scientists develop new treatments for the illness.

August 7, 2014. Montana State University researchers have made a significant contribution to the understanding of a new field of DNA research, with the acronym CRISPR, that holds enormous promise for fighting infectious diseases and genetic disorders. The MSU-led research provides the first detailed blueprint of a multi-subunit "molecular machinery" that bacteria use to detect and destroy invading viruses.

August 8, 2014. A research team at Trinity College Dublin, led by Dr. Martin Caffrey, used X-ray crystallography to gain new insights into the cellular structure and machinery of the Pseudomonas aeruginosa bacterium, creating a kind of structural "blueprint" that will aid scientists in pinpointing weaknesses that can be employed for treatment.

August 19, 2014. Ravi Acharya of the University of Bath and colleagues have reported the first crystal structure of the Clostridium difficile surface protein Cwp84. This cysteine protease enzyme is found on the surface of the bacterium and assists with production of the microbe's surface layer, which is likely to play an essential step in the colonisation of the human gut.

August 20, 2014. To commemorate the 100th anniversary of a revolutionary technique that underpins much of modern science, Chemical & Engineering News  magazine last week released a special edition on X-ray crystallography: its past, present and a tantalizing glimpse of its future. C&EN is the weekly news magazine of the American Chemical Society (ACS), the world's largest scientific society.

August 20, 2014. Israeli crystallographer Ada Yonath shared the 2009 Nobel prize in Chemistry for her work on the ribosome, a protein-building structure central to life found in all living cells. Curator of the University of Melbourne Chemistry Cultural Collection and researcher Dr. Renee Beale spoke to Professor Yonath after a public lecture in Melbourne about her upbringing in Israel and how it set her up for a life in science.

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Andrew D. Mesecar
Walther Professor of Cancer Structural Biology-Biochemistry
Department of Chemistry
Purdue University

The main interest of the Mesecar lab is the Structure & Function of Enzymes of biomedical importance. One of their fundamental goals is to gain a deeper understanding into the roles of protein dynamics and conformational changes in the molecular recognition and catalytic processes and to exploit this knowledge for the design of small molecule drugs that target these enzymes.

They are currently studying the structure and function of enzymes involved in cancer chemoprevention, cancer cell proliferation and bacterial and viral pathogenesis. They are actively involved in the discovery of both natural and synthetic compounds that can be used as anti-cancer, anti-viral and anti-bacterial therapeutics, as well as compounds that can prevent cancer and promote cell longevity.

Current projects in the lab include: (1) the roles of deubiquitinating enzymes (DUBs) in cancer and antagonism of the innate immune response and targeting DUBs for anti-cancer and antiviral drug development; (2) regulation of the Keap1-Cul3-Rbx1 E3 Ubiquitin ligase system in regulating the cellular concentrations of the transcription factor Nrf2 and hence activation of the anti-oxidant response element (ARE); (3) the structure, function and evolution of coronavirus papain-like and 3C proteases and developing therapeutics targeted at these enzymes; and (4) determining the structure and mechanisms of bacterial (e.g. tuberculosis and anthrax) adenylyltrasferase enzymes in the CoA, NAD, FAD and menaquinone biosynthesis and evaluating these enzymes as potential drug targets.

Andy's group can be followed on Facebook and his passion for Purdue football can be seen in his Boilermaker commercial.

Global Virus Network (GVN) is an essential and critical defense against viral disease. It is a coalition comprised of the best virologists spanning more than 20 countries worldwide, all working to advance knowledge about how viruses make us sick and to develop drugs and vaccines to prevent illness and death. No single institution in the world has expertise in all viral areas. GVN brings the best medical virologists together to leverage individual strengths and to focus global teams of scientists on key scientific problems. The power of GVN lies in its global reach, the depth of its science, and its commitment to solving viral challenges facing the human population. No other entity exists like the GVN.

Structural basis for activity of highly efficient RNA mimics of green fluorescent protein. Warner, Katherine Deigan; Chen, Michael C; Song, Wenjiao; Strack, Rita L; Thorn, Andrea; Jaffrey, Samie R; Ferré-D'Amaré, Adrian R. Nature Structural & Molecular Biology. Aug2014, Vol. 21 Issue 8, p658-663. 6p. DOI: 10.1038/nsmb.2865.

The structure of Lactobacillus brevis surface layer reassembled on liposomes differs from native structure as revealed by SAXS. Kontro, Inkeri; Wiedmer, Susanne K.; Hynönen, Ulla; Penttilä, Paavo A.; Palva, Airi; Serimaa, Ritva. BBA - Biomembranes. Aug2014, Vol. 1838 Issue 8, p2099-2104. 6p. DOI: 10.1016/j.bbamem.2014.04.022.

Structure of RPA32 bound to the N-terminus of SMARCAL1 redefines the binding interface between RPA32 and its interacting proteins. Xie, Si; Lu, Yao; Jakoncic, Jean; Sun, Hongzhe; Xia, Jiang; Qian, Chengmin. FEBS Journal. Aug2014, Vol. 281 Issue 15, p3382-3396. 15p. DOI: 10.1111/febs.12867.

Pyrrolo[3,2-b]quinoxaline Derivatives as Types I_1/2 and II Eph Tyrosine Kinase Inhibitors: Structure-Based Design, Synthesis, and in Vivo Validation. Unzue, Andrea; Dong, Jing; Lafleur, Karine; Zhao, Hongtao; Frugier, Emilie; Caflisch, Amedeo; Nevado, Cristina. Journal of Medicinal Chemistry. Aug2014, Vol. 57 Issue 15, p6834-6844. 11p. DOI: 10.1021/jm5009242.

Two water-soluble copper(II) complexes: Synthesis, characterization, DNA cleavage, protein binding activities and in vitro anticancer activity studies. Lu, Jing; Sun, Qian; Li, Jun-Ling; Jiang, Lin; Gu, Wen; Liu, Xin; Tian, Jin-Lei; Yan, Shi-Ping. Journal of Inorganic Biochemistry. Aug2014, Vol. 137, p46-56. 11p. DOI: 10.1016/j.jinorgbio.2014.03.015.

Nitrogenase FeMo cofactor: an atomic structure in three simple steps. Einsle, Oliver. Journal of Biological Inorganic Chemistry. Aug2014, Vol. 19 Issue 6, p737-745. 9p.DOI: 10.1007/s00775-014-1116-7.

Mutagenesis Studies of the H5 Influenza Hemagglutinin Stem Loop Region. Antanasijevic, Aleksandar; Basu, Arnab; Bowlin, Terry L.; Mishra, Rama K.; Lijun Rong; Caffrey, Michael. Journal of Biological Chemistry. 8/8/2014, Vol. 289 Issue 32, p22237-22245. 9p. DOI: 10.1074/jbc.M114.572974.

X-ray vs. NMR structure of N-terminal domain of δ-subunit of RNA polymerase. Demo, Gabriel; Papoušková, Veronika; Komárek, Jan; Kadeřávek, Pavel; Otrusinová, Olga; Srb, Pavel; Rabatinová, Alžbeta; Krásný, Libor; Žídek, Lukáš; Sklenář, Vladimír; Wimmerová, Michaela. Journal of Structural Biology. Aug2014, Vol. 187 Issue 2, p174-186. 13p. DOI: 10.1016/j.jsb.2014.06.001.

Crystal structure of an antiviral ankyrin targeting the HIV-1 capsid and molecular modeling of the ankyrin-capsid complex. Praditwongwan, Warachai; Chuankhayan, Phimonphan; Saoin, Somphot; Wisitponchai, Tanchanok; Lee, Vannajan; Nangola, Sawitree; Hong, Saw; Minard, Philippe; Boulanger, Pierre; Chen, Chun-Jung; Tayapiwatana, Chatchai. Journal of Computer-Aided Molecular Design. Aug2014, Vol. 28 Issue 8, p869-884. 16p.DOI: 10.1007/s10822-014-9772-9.

Crystal structures of type III_H NAD-dependent D-3-phosphoglycerate dehydrogenase from two thermophiles. Kumar, S.M.; Pampa, K.J.; Manjula, M.; Hemantha Kumar, G.; Kunishima, Naoki; Lokanath, N.K. Biochemical & Biophysical Research Communications. Aug2014, Vol. 451 Issue 1, p126-130. 5p. DOI: 10.1016/j.bbrc.2014.07.075.

Book review: Stuff Matters: Exploring the Marvelous Materials that Shape our Man-Made World

     by Mark Miodownik
     Houghton Mifflin Harcourt Publishing, New York, 272 pp, ISBN: 978-0544236042.

Mark Miodownik's book, Stuff Matters, is a delightful approach to the history and the science of modern materials by a materials scientist. His structure and approach for the book is unique-unlike anything I've encountered yet in popular science nonfiction.

Miodownik starts with a black-and-white photograph of himself sitting at a table on the roof of his flat. Each chapter begins with a reproduction of that photograph, but with an arrow pointing to a different object and a label describing the object's composition. He offers a brief history of each material, laced with a personal anecdote or two, and often accompanied by a hand-drawn illustration of its molecular composition.

Perhaps the most entertaining chapter is that on chocolate. A self-professed "chocaholic," Miodownik's passion for the popular food is evident. Given the fame of Swiss chocolate, I had always thought that the solid bar form was invented in Switzerland, but it was, in fact, an English firm called Fry and Sons that first produced "eating chocolate." However, this chocolate, which had thirty percent sugar added, was too bitter. The Swiss were the first to use milk to combat this bitterness, essentially inventing what we now know as milk chocolate. They used the powdered milk recently introduced by Nestlé, a company that was attempting to give a localized commodity with virtually no shelf-life a transportable quality and a longer shelf-life.

It was quite fortunate for the Swiss that Nestlé was pioneering powdered milk at the same time that Fry's introduced their too-bitter eating chocolate. Adding regular non-powdered milk to the chocolate would have been disastrous. Chocolate powder is hydrophilic, and will absorb water; however, because fat and water do not dissolve in each other (fat is hydrophobic), the chocolate powder would eject its fat coating, making the resulting liquid lumpy and generally regarded as unappetizing. One can only imagine the differences in our modern world if powdered milk had never been developed.

Miodownik's passion for the subject (of) matter as a materials scientist is evident in his prose, and makes the book a quick and easy read. There is very little technical jargon that might impede the enjoyment of the book by someone not trained in materials science, or even the sciences in general. Miodownik is a man who loves what he does, and sees his work in the world around him. This book is a testament to his desire to inspire excitement for materials science in those around him as well.