bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress of robotized systems for crystallography for beamlines and laboratories
Authors: Ferrer Jean-Luc , Vernede Xavier , Sallaz-Damaz Yoann , Berzin Christophe , Pirocchi Michel , Borel Franck , Larive Nathalie
Published: November 2015

Development of 6-axis robotic arm based systems for protein crystallography automation is now expending rapidly. From the seminal work accomplished on beamline FIP-BM30A (ESRF) in 2000' to the present developments, robot based systems significantly changed the crystallography experiment strategy. They open possibilities for new strategies, give a high flexibility to the experimental setup, and make automation and remote control much easier. The robotized platform on which are based our present developments, named G-Rob, plays as a fully integrated, multi-purpose automated and remotely controlled diffractometer for beamlines and laboratories. G-Rob integrates several functions: classical sample changer; goniometer for frozen samples or capillaries [1], including frozen sample transfer from a storage Dewar; crystallization trays handling for in situ screening and data collection on crystallization plates and microchips [2]; powder diffraction; beam monitoring; on line crystal fluorescence/absorption; crystal harvesting; Etc. Thanks to its tool changer, the robot arm can go automatically from one application to another. G-Rob can be easily upgraded with new functions. Several G-Rob systems, both at synchrotrons (ESRF, LNLS, BNL) or as laboratory in-house systems (EPFL, CBS) are now available for the crystallography community. Among the last results obtained with G-Rob are: (i) Automated structure resolution at room temperature, for the analysis of protein dynamic; (ii) Automated structural screening for the fragment based drug design strategy. New functions are also under development, such as the remote controlled robotized crystal harvesting [3]. Such manipulations of individual crystals with the robot closes the gap for fully remote, and in the future fully automated, operation of crystallography pipeline.
Crystal structure of the human COP9 signalosome
Authors: Bunker Richard , Lingaraju Gondichatnahalli , Thomä Nicolas
Published: November 2015

The COP9 signalosome (CSN) is a multifunctional ~350 kDa eight-protein complex with highly-specific isopeptidase activity, which regulates the vast cullin-RING family of ubiquitin ligases (CRLs). Ubiquitin ligases direct target-specific ubiquitination and are involved in a multitude of regulatory processes, ultimately linked to protein turnover by the proteosome. Humans have a repertoire of approximately 240 CRLs, more than any other ubiquitin ligase family. The entire human CSN has been structurally characterised de novo using low-resolution (4-Å) X-ray crystallography. The crystallographic analysis was complicated by rotational pseudo-symmetry and twinning, non-isomorphism as well as the absence of experimental phase information beyond ~8 Å resolution. Details of the structure determination procedures, which combined a cluster compound-based phasing strategy, analysis of seven differentially substituted selenomethionyl derivatives, multi-crystal averaging among non-isomorphous data sets with a multi-crystal co-refinement approach, will be described. Some implications of the structure and insight into the regulation of CSN will also be presented.
Stop! Don't throw that crystal away!
Authors: Powell Harold , Leslie Andrew , Johnson Owen , Evans Philip , Murshudov Garib
Published: November 2015

We have developed methods for processing area detector data collected from samples containing several crystal lattices, and implemented these into the data processing program Mosflm and its GUI iMosflm [1]. In particular we have extended the following processes: (1) modified autoindexing routines recognize different lattices and display this information in iMosflm in a clear and concise way, allowing the user to choose how to proceed. (2) multiple lattice information is used to determine which data are used in refinement of crystal parameters and which (e.g. overlapped reflections) should be excluded. (3) observations are integrated in each lattice and flagged in the output reflection file (written in the MTZ format) to indicate whether they arise from a single lattice or from overlapped reflections from multiple lattices. The choice of lattice in the latter two stages of data processing is made simple in iMosflm. The information regarding reflection overlap can now be processed correctly in the merging and scaling steps by the programs Feckless, Pointless and Aimless [2]. The refinement program RefMac [3] has been modified to make use of the extra information from multiple lattices. We will discuss these improvements to processing and present early results from their implementation.
Ultrafast Dynamical Study Using Time-resolved Laue Diffraction
Authors: Thekku Veedu Sreevidya
Published: November 2015

Electron transfer reactions are fundamental processes in chemistry and also in biology [1-3]. Light harvesting complexes are functional centers in plants where sunlight is converted into chemical energy. In this, optical excitation in a chromophore unit leads to the transfer of electrons within the system. However, due to the complexity of the biological photo-reaction centre, recent spectroscopic efforts have concentrated on a smaller chemical model which share characteristic with their biological counter parts. A promising model is the so-called D-A (donor-acceptor) systems, which are chemically synthetic molecules with electron transfer capabilities. The electrical conductivity is a function of the optical state of the system. An optically switching diode is an interesting application of donor-acceptor molecules. We aimed to determine photo-induced structural changes in Pyrene-N,N-dimethylaniline (PyDMA). Static structures for many molecules are available at high resolution but the mechanism by which these molecules function and the structures of intermediate states often remain elusive. Knowledge of the geometry of molecular excited states at atomic resolution is crucial for a full understanding of photo-induced chemical processes. Time-resolved X-ray diffraction (TR-XRD) using polychromatic synchrotron radiation allows a detailed study of the time evolution of structural intermediates and short living states of chemical systems at wide range of time-scales, drawing a complete picture of the photo-induced charge transfer process. Investigation of photo-excitation processes in molecular single crystals, where the initial photo-excitation processes occur on extremely short time-scales (femto-/picosecond time domain) and have been in the focus of scientific investigations due to their possible applications, e.g. as optical switches.
High-pressure X-ray Diffraction Study of SrSi2O2N2:Eu2+
Authors: Ermakova Olga , Paszkowicz Wojciech , Kaminska Agata , Barzewska Justyna , Szczodrowski Karol , Grinberg Marek , Nowakowska Malgorzata , Minikayev Roman , Liu Ru-Shi , Suchocki Andrzej
Published: November 2015

SrSi2O2N2oxynitride crystallizes in the P1 space group [1]. This compound is an excellent host for phosphors, due to its superior thermal and chemical stability and large energy bandgap. Eu-doped SrSi2O2N2can be used in green LEDs, and as a green component in phosphor mixtures; it is suitable, in particular, for white LEDs. For application in LEDs, the most important feature of SrSi2O2N2:Eu2+is the intense broadband luminescence at about 530 nm. In this study, high-pressure X-ray powder diffraction (XRD) experiments are used in order to experimentally determine, for the first time, the equation of state (EOS) of SrSi2O2N2:Eu2+. The studied sample, with Eu content of 2% was prepared by solid state reaction. The in situ XRD experiment was performed at the I711 beamline of MAXII synchrotron (Lund, Sweden) for a sample mounted in a diamond anvil cell, using hydrostatic compression conditions. The applied X-ray wavelength was 0.9917 Å. In the pressure range studied (up to 9.6 GPa) the triclinic structure is found to be conserved. Lattice parameters a, b and c decrease smoothly but slightly anisotropically as a function of applied pressure, whereas the angles α, β and γ vary marginally. The material is the most compressible in the b direction and the least compressible in the a direction. Angles α and γ are almost constant whereas the value of β angle slightly increases with rising pressure. The variation of unit cell volume with pressure served for determination of the Birch-Murnaghan EOS: the resulting bulk modulus value is 103(5) GPa. The present bulk modulus value is by 22% smaller than those reported for other oxonitridosilicates such as SrSiAl2O3N2and Ce4[Si4O4N6]O (131.9(1) GPa and 131(2) GPa, respectively) [2].
Hydrogen-rich Inclusion Compounds at High-pressure
Authors: Donnelly Mary-Ellen , Bull Craig , Frantzana Athina , Klotz Stefan , Loveday John
Published: November 2015

Molecular hydrogen (H2) has been proposed as an alternative fuel source for vehicles. Though H2has many benefits, such as clean combustion and the highest known energy density by mass, there are issues in how to store it in a safe and cost effective way. One solution is to store hydrogen in a chemical compound, and gas clathrates (crystalline inclusion compounds) have shown promising results. Pressure provides a powerful means to tune the properties of such compounds and its effects on potential hydrogen storage materials are widely explored. We have recently developed a hydrogen-compatible gas loader for the Paris-Edinburgh press, which enables the loading of high density hydrogen into a clamp with a sample volume suitable for neutron diffraction experiments using the Paris-Edinburgh press [1]. Neutron diffraction is the technique of choice for such materials since it can reveal the location and occupancy of the hydrogen sites. We will present recent data from high-pressure neutron diffraction experiments on hydrogen hydrates as well as other clathrate forming systems like urea and hydroquinone.
Reciprocal space mapping of silver nanoparticle array re-assembly and oxidation
Authors: Jergel Matej , Siffalovic Peter , Vegso Karol , Benkovicova Monika , Vojtko Andrej , Majkova Eva , Lee Hsin-Yi , Ku Ching-Shun , Lin Man-Ling , Jeng U-Ser
Published: November 2015

Self-assembled metal oxide nanoparticle layers have attracted much attention recently due to potential applications in sensors. Here we report on a UV/ozone-driven re-assembly and oxidation of a self-assembled silver nanoparticle bilayer deposited by a modified Langmuir-Schaefer technique that was probed in-situ by simultaneous measurements of the small- and wide-angle X-ray scattering at grazing incidence (GISAXS, GIWAXS). The experiments were performed at BL23A endstation of NSRRC, Taiwan. Four distinct stages of the system response to the UV/ozone treatment were identified. In the first stage 0-120 s, a gradual extinction of Bragg rods and the nanoparticle short-range order due to a gradual surfactant removal is observed in GISAXS that is connected with an array densification and order improvement obeying the paracrystal model in the shrinking self-assembled regions. In the second stage 120-360 s, the original self-assembly goes to a total extinction while the integral intensity of Ag 111 diffraction in GIWAXS starts to decrease, suggesting the total surfactant removal. No nanoparticle short-range order is observed in stage III 360-730 s where AgO monoclinic phase due to the nanoparticle surface oxidation appears and pure Ag phase disappears. The initial AgO unit cell volume corresponding to the unstrained phase gradually expands by 4.6 % to the end of stage III. In stage IV 730-2000 s (end of measurements), new Bragg rods appear in GISAXS, suggesting a nanoparticle agglomeration with a typical correlation length of approximately 240 nm that was confirmed by ex-situ atomic force microscopy. The agglomeration does not reach saturation even after 2000 s while the AgO phase remains stable. These results have direct implications for tailored preparation of advanced sensors based on metal oxide nanoparticles. The work was supported by the projects APVV-0308-11, VEGA 2/0041/11, SAS-NSC JRP 2011/05, SAS-TUBITAK JRP 2013/6, COST MP1203 and COST CM1101.
Structure investigations of nanocrystalline glass ceramics by ASAXS
Authors: Hoell Armin , Raghuwanshi Vikram , Rüssel Christian
Published: November 2015

Glass ceramics containing fluoride crystals such as BaF2 or CaF2 with crystallite sizes in the range from 5 to 100 nm are potential candidates for numerous photonic applications. Glass ceramics containing rare-earth-doped fluoride crystals are candidates for laser materials. The size distribution plays an important role and often a narrow size distribution is required for photonic applications. In the last years a hindered growth effect leading to a more narrow size distribution was observed during the crystallization of BaF2 as well as CaF2 nanocrystals in oxy-fluoride glasses. The aim of this study is a detailed quantitative structural and nano-chemical analysis of the formation of BaF2 or CaF2 in two glass ceramics by Anomalous Small-Angle X-ray Scattering (ASAXS) to reveal and understand the mechanism of hindered growth. Nanocrystals of BaF2 precipitate during heat treatment of a silicate glass of composition 69.6SiO2-7.52Al2O3-15.04K2O-1.88Na2O-4BaF2-2BaO. X-ray diffraction measurement proved the formation of BaF2 crystals in the glass matrix. High resolution TEM showed the formation of spherical particles of sizes in range from 10-40 nm surrounded by a layer enriched with SiO2. SAXS reveal the growth of nanocrystals with increasing annealing time and temperatures. ASAXS experiments are done at four energies close to the Ba-L3 X-ray absorption edge (5247eV). The ASAXS curves for the sample annealed at 5400C for 20h revealed a spherical core-shell model. It turned out that the layer surrounding the BaF2 crystals is enriched with SiO2. Sizes and compositions of these layers are analyzed quantitatively. Furthermore, the ASAXS analysis reveals the presence of very small nucleates of size of about 3 nm in the as melted glass sample already [1]. A precipitation of CaF2 nanoparticles takes place during heat treatment of glasses of composition 7.65Na2O–7.69K2O–10.58CaO–12.5CaF2–5.77Al2O3–55.8SiO2 up to 40 hours. SAXS experiments and especially ASAXS near the Ca-K edge proves the formation of CaF2 nanoparticle surrounded with SiO2 enriched layers, quantitatively. The ASAXS effect is very pronounced at this untypical low energy for ASAXS studies at the Ca-K edge. The ASAXS result reveals crystal sizes between 10-20 nm surrounded by a shell of lower electron density. Additional very small heterogeneities are found after long annealing with diameters of about 1.6 nm [2].
3D grain orientation mapping of nanocrystalline materials in the TEM
Authors: Schmidt Soeren , Larsen Peter , Huang Xiaoxu
Published: November 2015

Nanocrystalline materials (i.e. polycrystalline aggregates where the individual crystallites/grains or particles have sizes below 100 nm) are formed through various processes ranging from mechanical treatments of bulk materials, to electrodeposition of thin films and coatings to aggregation of nanoparticles. The materials constitute one of the most rapidly growing new classes of materials and exhibit enhanced properties, see e.g. [1,2], ranging from high strength and wear resistance, to unique functional characteristics, which open up a large spectrum of applications e.g. for micro- and nano-electro-mechanical systems (MEMS and NEMS). Consequently, materials models tend to be based only on simple observables such as a 2D crystalline projection or an average grain/particle size. Motivated by this, a new and non-destructive technique called "3D-Orientation Mapping in TEM" (3D-OMiTEM) was developed and it was demonstrated that both orientation and 3D morphology of ~1000 individual nanograins could be measured with spatial and angular resolutions of 1 nm and 1 degree [3]. Notably, the foil may have five or more grains stacked on top of each other in the thickness direction. Technically speaking, 3D-OMiTEM is based on conical-scanning dark-field imaging. By recording images at a series of different beam and sample tilt angles it is possible to reconstruct the complete 3D orientation map of nanograins or nanoparticles. With the availability of 3D-OMiTEM crystallographic orientation relationships, interface curvatures, 3D connectivity between nanograins or nanoparticles as well as evolution of 3D structures e.g. during heat treatments or deformation steps, can be addressed for the first time in nanocrystalline materials. An overview of the methodology and latest results is given.
Silver(I) and Lead(II) Complex Formation with Thiolates
Authors: Jalilehvand Farideh , Sisombath Natalie , Leung Bonnie , Mah Vicky
Published: November 2015

Lead toxicity is frequently attributed to the displacement of essential metals such as zinc. Lead(II) ions mainly inhibit the enzymatic activity of ALAD, a key zinc-containing metalloenzyme in the heme biosynthetic pathway with much higher affinity to bind to Pb(II) than Zn(II) ions via its cysteinyl residues. Also for silver(I) ions the interaction with thiol-containing species such as cysteine and glutathione plays a key role in bacterial inactivation and Ag(I) antimicrobial activity. We will present the results of our investigations on Pb(II) and Ag(I) complex formation with small thiol-containing molecules of biological interest such as cysteine, penicillamine, N-acetylcysteine and glutathione, using a combination of different techniques, including X-ray absorption fine structure (XAFS) spectroscopy, multinuclear NMR (207Pb, 109Ag) and X-ray crystallography.
A size comparison of the lanthanoid(III) and actinoid(III) ionic radii
Authors: Lundberg Daniel
Published: November 2015

Using lanthanoid(III) ions as non-radioactive substitutes for the actinoid(III) ions in model compounds is commonplace in many nuclear research areas. For instance, highly radioactive americium(III) ions are often replaced by europium(III) ions, found at the same position in the lanthanoid series. There is, however, no structural evidence to support this replacement, a fact that proponents in many fields do not consider. By carefully comparing the available data sets, it becomes obvious that the visual overlap in the periodic table does not reflect the true ionic radii of these elements at all. Here, using structural data from both solution and solid state, we present a comparative study of the ionic radii of the two inner transition metal series.
Structural basis for the evolution of vancomycin resistance D,D-peptidases
Authors: Stogios Peter , Meziane-Cherif Djalal , Evdokimova Elena , Courvalin Patrice , Savchenko Alexei
Published: November 2015

Emergence of high-level resistance to the last resort glycopeptide antibiotic vancomycin in Enterococcus spp. and its spread to methicillin-resistant Staphylococcus aureus is a public health threat. Resistance to vancomycin is due to substitution of the D-Ala-D-Ala terminus of cell wall precursors, which forms the antibiotic target, by D-Ala-D-Lac or D-Ala-D-Ser of low binding affinities. Resistance also requires depletion of the normal precursors catalyzed by the zinc-dependent D,D-peptidases VanX and VanY acting on dipeptide (D-Ala-D-Ala) or pentapeptide (UDP-MurNac-L-Ala-D-γ-Glu-L-Lys-D-Ala-D-Ala), respectively. Some resistance operons encode VanXY D,D-peptidase acting on both substrates. Van D,D-peptidases represent attractive targets for combinational antimicrobial therapies to curb resistance; however, the molecular basis of their specificity remains poorly understood, hindering development of potent inhibitors. Therefore we undertook detailed structure-function analysis of VanXY and VanY enzymes. Obtained structural information revealed the substrate-binding site of VanXYC as an extended cavity suitable for binding of di- or pentapeptides, contrasting with previous results showing that VanX contains a small, shallow active site. Biochemical and mutagenesis analysis identified a mobile cap over the catalytic site of VanXYC as the key structural element involved in a switch between di- and pentapeptide hydrolysis. The structures also provided the molecular basis for selectivity towards Van-susceptible peptidoglycan precursors. Overall, this study illustrates the adaptability of the D,D-peptidase fold in response to antibiotic pressure via evolution of particular structural elements that modulate substrate specificity. The results open new opportunities for structure-guided development of Van D,D-peptidases specific inhibitors as glycopeptides adjuvants. This project has been funded by NIAID under Contracts No. HHSN272200700058C and HHSN272201200026C.
Type II topoisomerases as targets for rational drug design
Authors: Laponogov Ivan , Veselkov Dennis , Umrekar Trishant , Crevel Isabelle , Pan Xiao-su , Fisher L Mark , Sanderson Mark
Published: November 2015

Bacterial drug resistance is a growing and now widely recognised threat and the limited number of new antibacterials developed in the recent years is a serious matter of concern. One of the approaches to combat this growing threat is to investigate the mechanisms of action of currently available antibacterials, as well as studying the way that bacteria are currently developing drug resistance and may potentially in the future develop drug resistance to known remedies. This knowledge should in turn be used in rational drug design and the general development of the appropriate frameworks for combating bacteria, while at the same time keeping the negative side effects of the drugs to the acceptable minimum. This is especially important when both bacteria and humans share similar drug targets, such as is the case for topoisomerases (in humans, the latter are also targeted by anti-cancer drugs). Our main protein targets of interest are type II topoisomerases which are involved in regulation of the DNA supercoiling in both bacteria and eukaryotes and also in decatenation of bacterial daughter chromosomes during cell division. Type II topoisomerases are performing their biological action by binding the double stranded DNA (called G-segment or Gate-DNA), temporarily cleaving it and passing another double stranded DNA (called T-segment) in the ATP-assisted process via the cleavage region thus changing the linking number in steps of12. After that the G-segment is resealed and released. Several drugs were found to be able to disrupt this process ultimately resulting in the cell death (thus having anti-bacterial or anti-cancer action). Here we present our studies of the protein-DNA-drug interactions which are involved in the action of currently clinically used quinolone antibacterials as well as their newly developed alternatives (such as quinazolinediones) in relation to their mechanism of action and already established potential routes for developing drug resistance in bacteria. We present the results for different pathogens (including, but not limited to Streptococcus pneumoniae and Klebsiella pneumoniae) and also compare the configuration of the active site with the one from type II topoisomerases from a human organism.
Crystal structures of hFPPS in complex with novel anticancer drug leads
Authors: Park Jaeok , Leung Chun , Lin Yih-Shyan , De Schutter Joris , Tsantrizos Youla , Berghuis Albert
Published: November 2015

Human farnesyl pyrophosphate synthase (hFPPS) produces farnesyl pyrophosphate, an isoprenoid required for a variety of essential cellular processes. Inhibition of hFPPS has been well established as the mechanism of action of the nitrogen-containing bisphosphonate (N-BP) drugs, currently best known for their anti-bone resorptive effects. Recent investigations indicate that hFPPS inhibition also produces potent anticancer effects both in vitro and vivo: N-BPs inhibit proliferation, motility, and viability of tumor cells, and act in synergy with other anticancer agents [1,2]. However, the physicochemical properties of the current N-BP drugs seriously compromise their full anticancer potential in non-skeletal tissues. They show poor membrane permeability and extreme affinity to bone, due mainly to their highly charged bisphosphonate moiety, which mimics the pyrophosphate of the substrates of hFPPS. Both the substrates and N-BPs bind to hFPPS via Mg ion-mediated interactions between their pyrophosphate/bisphosphonate moiety and two aspartate-rich surfaces of the enzyme's active site cavity. Recently, we took a structure-guided approach to develop bisphosphonates with higher lipophilicity for enhanced uptake into non-skeletal tissues. Surprisingly, some of the new compounds were found to bind to hFPPS even in the absence of Mg ions. Crystal structures of hFPPS in complex with a representative compound revealed that this bisphosphonate binds to the enzyme's active site in the presence of Mg ions, but also to a nearby allosteric inhibitory site in their absence. Furthermore, removal of a phosphonate group from the bisphosphonate moiety of this compound resulted in an inhibitor that binds exclusively to the allosteric site. Based on the crystal structures with these lead compounds, we generated of a novel class of non-bisphosphonate, allosteric inhibitors of hFPPS with superior physicochemical properties than those of the current N-BP drugs for broader tissue distribution.
Structure-based drug design against Trypanosoma brucei methionyl-tRNA synthetase
Authors: Koh Cho Yeow , Nguyen Jasmine , Shibata Sayaka , Zhang Zhongsheng , Ranade Ranae , Gillespie J. Robert , Hodder Peter , Pedro-Rosa Laura , Bannister Thomas , Buckner Frederick , Verlinde Christophe , Fan Erkang , Hol Wim
Published: November 2015

Infection by the protozoan parasite Trypanosoma brucei causes human African trypanosomiasis, commonly known as sleeping sickness. The disease is fatal without treatment; yet, current therapeutic options for the disease are inadequate due to toxicity, difficulty in administration and emerging resistance. Therefore, methionyl-tRNA synthetase of T. brucei (TbMetRS) is targeted for the development of new antitrypanosomal drugs. We have recently completed a high-throughput screening campaign against TbMetRS using a 364,131 compounds library in The Scripps Research Institute Molecular Screening Center. Here we outline our strategy to integrate the power of crystal structures with high-throughput screening in a drug discovery project. We applied the rapid crystal soaking procedure to obtain structures of TbMetRS in complex with inhibitors reported earlier[1] to approximately 70 high-throughput screening hits. This resulted in more than 20 crystal structures of TbMetRS·hit complexes. These hits cover a large diversity of chemical structures with IC50 values between 200 nM and 10 µM. Based on the solved structures and existing knowledge drawn from other in-house inhibitors, the IC50 value of the most promising hit has been improved. Further development of the compounds into potent TbMetRS inhibitors with desirable pharmacokinetic properties is on-going and will continue to benefit from information derived from crystal structures.
Structural insight into the function and anti-TB pro-drug activation by KatG
Authors: Hersleth Hans-Petter , Zhao Xiangbo , Magliozzo Richard , Andersson K. Kristoffer
Published: November 2015

Catalase-peroxidase (KatG) is a dual functional enzyme with both catalase and peroxidase activity. KatGs protect aerobic microorganisms from oxidative damage through their high catalase activity, and in Mycobacterium tuberculosis (M.tb.) KatG's peroxidatic activity is central in converting the anti-tuberculosis (TB) pro-drug isoniazid (INH) into an active bactericidal molecule in vivo. There are several antibiotics currently in use to treat TB with INH being one of the first anti-TB agents. A central goal is to understand the catalytic function of M.tb. KatG in drug activation and how mutations in KatG found in INH-resistant strains interfere with this process. One of the most common INH-resistant M.tb. strains has the KatG[Ser315Thr] mutation, previously reported to cause narrowing of a substrate access channel. We have now solved the structure of another mutant [Asp137Ser], which shows enhanced INH-activation ascribed to an enlarged access channel. This study demonstrates that altering the dimensions of the bottleneck in the substrate access channel in KatG can impede or enhance INH peroxidation rates relative to the WT enzyme.
Structural characterization of aminoglycoside modifying enzyme ANT(2")-Ia
Authors: Bassenden Angelia , Rodionov Dmitry , Sabet-Kassouf Nilu , Haji Tahereh , Shi Kun , Berghuis Albert
Published: November 2015

Aminoglycosides are a class of broad-spectrum antibiotics used in the treatment of serious Gram-negative bacterial infections, they target the 16S RNA subunit and upon binding cause errors in translation, eventually inducing a bactericidal effect [1]. Aminoglycoside nucleotidyltransferase (2")-Ia (ANT(2")-Ia) is an aminoglycoside modifying enzyme that prevents aminoglycosides from binding to the ribosomal subunit, making this enzyme a principle candidate structure-based drug design [2]. Characterization of ANT(2")-Ia has been proven to be difficult due to the low stability and solubility of overexpressed protein, where 95% of the protein being expressed is in the form of inclusion bodies [3]. We describe a protocol that has lead to successful expression and purification of ANT(2")-Ia. A successful enzymatic assay has also been adapted and the protein is active and stable under these conditions with a specific activity of 0.14 U/mg. Furthermore, nuclear magnetic resonance (NMR) studies have allowed for the assignment of 144 of the 176 non-proline backbone residues. Substrate binding NMR experiments have shown unique global chemical shift perturbations upon binding ATP and tobramycin, suggesting unique binding sites for each substrate. Structural determination of ANT(2")-Ia using NMR in conjunction with x-ray crystallography can be utilized in order to develop small molecules that will act as more effective aminoglycosides in order to inhibit ANT(2")-Ia from binding and modifying these antibiotics.
Hybrid photon-counting detectors accelerating synchrotron and laboratory science
Authors: Schulze-Briese Clemens
Published: November 2015

Since their introduction in 2007, single-photon-counting PILATUS hybrid pixel detectors and MYTHEN micro-strip detectors have transformed synchrotron research by enabling new data acquisition modes and even novel experiments. At the same time data quality has improved due to the noise-free operation and the direct conversion of the X-rays, while millisecond readout time and high-frame rates allow for hitherto unknown data acquisition speed and efficiency. Instant retrigger technology, introduced in 2012 with the PILATUS3 further improves the count-rate capabilities to 107 photons/sec/pixel, allowing single photon counting at brightest synchrotron beamlines. On the other hand, the unique properties of these detectors have also been explored to improve and accelerate diffraction and scattering experiments in the laboratory. The noise-free operation is a key advantage in combination with the low-flux laboratory sources, allowing for high-throughput and optimal data quality. The modular architecture of the detectors and the vacuum-compatibility of the PILATUS detector modules are ideal prerequisites to design specific detector solutions. In-vacuum operation is ideally suited to eliminate all background arising from windows and air, resulting in optimal signal-to-noise ratio. Furthermore, the lowest accessible X-ray energy is no longer limited by windows and air absorption but rather by the beamline spectrum and the detector. The minimal X-ray energy compatible with noise-free counting for the PILATUS is below 2 keV. With EIGER, hybrid pixel detectors will enter into a new realm of spatial and temporal resolution. Continuous read-out with frame rates up to 3000 Hz and a pixel size of 75 µm are ideally suited for all scanning type of imaging experiments, time-resolved and high-throughput experiments as well as for outrunning radiation damage. A short overview of the novel aspects of the detector technology will be given. The main emphasize of the presentation will be on the science enabled by the combination of advanced source, optics and detector instrumentation.
In-house energy resolved Laue XRD measurements with a Pilatus detector
Authors: Kurdzesau Fiodar , Simonov Arkadiy , Schneebeli Matthias , Pilipp Volker , Weber Thomas
Published: November 2015

The use of 2D position and energy sensitive hybrid pixel Pilatus detectors allows performing energy-dispersive analysis of Bragg reflections [1]. This significantly improves the classical Laue experiments enabling the unique determination of the crystal lattice and resolving the higher order harmonics. It allows quantitative crystal structure determination using the Laue method without having any priory information about the crystal [2]. Such energy-dispersive Laue diffraction (EDLD) experiments can be performed with a white X-ray beam either from a synchrotron source or from conventional X-ray tubes. The second approach looks less profitable due to its lower irradiation intensity, but this can be compensated considering the better control of white beam spectra by applying different voltage/current settings during the tube operation. Thus, one can efficiently combine the primary beam and XRD measurements using the same Pilatus detector. This allows the implementation of the energy resolved (color Laue) method for any conventional XRD diffractometer equipped with a Pilatus detection system. In the present work EDLD experiments with a conventional X-ray tube were combined with corresponding primary beam measurements using a 300K Pilatus detector tuned for operation within an energy range of 4-25 keV at energy resolution <0.12 keV. Such a combination simplifies several data correction procedures (the spectral intensity distribution, the sample absorption etc.) significantly. Following our developed intensity correction protocols the structure refinement of a reference quartz sample could be achieved with R-factor <0.10. Possible applications of this method (e.g. quantitative XRD studies with stationary crystals) and the details for its further development will be discussed.
Current and future detector developments at the Swiss Light Source
Authors: Schmitt Bernd , Bergamaschi Anna , Cartier Sebastian , Dinapoli Roberto , Greiffenberg Dominic , Johnson Ian , Mozzanica Aldo , Shi Xintian , Smith Julia , Tinti Gemma
Published: November 2015

The detector group of the Swiss Light Source (SLS) at the Paul Scherrer Institut (PSI) has a long history of x-ray detector developments for synchrotrons. Initially these detectors were all single photon counting systems. In the last years the focus at PSI was moving towards charge integrating systems mainly driven by the detector needs for the upcoming XFELs. Charge integrating systems however also solve some of the problems of single photon counting systems. Charge integrating systems have an almost infinite linear count rate capability, allow systems with smallest pixel sizes and for low photon energies. In this presentation we give an overview of the detector developments at PSI and focus on Jungfrau, Mönch and Eiger. Eiger is a single photon counting system specifically developed for high frame rates. It has a 75 micron pixel size and can run at frame rates up to 24 kHz. A 9M Eiger detector will be installed in a few months at the cSAXS beamline of the SLS. Jungfrau uses the same sensor as Eiger (about 4cm x 8 cm with a pixel size of 75 microns). It has a charge integrating architecture with dynamic gain switching to achieve a dynamic range of 10^4 photons (at 12 keV). With a frame rate of up to 2 kHz Jungfrau is currently being developed for applications at both XFELs and synchrotrons. 16M Jungfrau detectors are foreseen at the SwissFEL. Mönch is currently a research project. A first prototype with 160x160 pixels and a pixel size of 25 microns was designed and is currently characterised. It offers the smallest pixel size of current hybrid pixel detectors and also has a very low noise allowing hybrid pixel detectors to be used down to about 400eV. We present measurement results for Jungfrau, Mönch and Eiger and give an outlook on future possible systems.
Deprotonation of resorcinarenes and novel ammonium salt complexes
Authors: Beyeh Ngong , Valkonen Arto , Pan Fanfang , Rissanen Kari
Published: November 2015

The bowl shape cavity of resorcinarenes usually stabilized by four intramolecular hydrogen bonds offers an interesting array of binding modes such as C–H...π and cation...π interactions to recognize a variety of guests. The multiple hydroxyl groups can participate in a series of intermolecular hydrogen bonds with guest molecules. This unique cone conformation of resorcinarenes has led to the synthesis of many receptors with convergent arrangement of binding sites suitable for molecular recognition in many applications. Unfunctionalized resorcinarenes are known to easily form molecular complexes with guests of varying shapes and sizes. Amines are very common bases used in many catalytic processes. A good example is the use of amines as bases in the alkylation and acylation of resorcinarenes leading to cavitands, carcerands, hemicarcerands and velcrands. The use of amines in such reactions is to deprotonate the resorcinarene hydroxyl groups, hence facilitating the alkylation and acylation processes. The subsequently protonated ammonium cation then forms interesting supramolecular complexes with the anionic and dianionic resorcinarenes. Furthermore, secondary and tertiary ammonium salts possess hydrogen bond donating -NH2 and -NH respectively and these can further enhance their complexation through intermolecular hydrogen bonds. Here we present our recent examples of supramolecular assemblies resulting from the deprotonation of resorcinarenes by mono- and dibasic amines. Also, our latest supramolecular co-crystals between resorcinarenes as the receptors and a series of secondary and tertiary mono- and diammonium cations are illustrated.
"Organic Fluorine" and its Importance in Crystal Engineering
Authors: Roy Choudhury Angshuman , Kaur Gurpreet , Karanam Maheswararao , Patel Sandhya
Published: November 2015

The phrase "Organic fluorine" [1] was introduced by Dunitz and Taylor in 1997 to identify the C–F bonds in organic systems. Different research groups have used the phrase to glorify or deny the influence of C–F bond in crystal lattices. Once Dunitz stated that "Organic Fluorine: Odd Man Out" and Howard et al. questioned the role of "Organic fluorine" in crystal engineering. While some researchers have refuted the role of "organic fluorine" in crystal packing; the others indicated the importance of the interactions involving the same group. A number of publications have shown the importance of "Organic fluorine" in influencing crystal packing. We have been interested in the area of weak interactions in organic solid state chemistry since 1999 [2]; especially interactions involving "Organic fluorine". The study is being conducted following a systematic approach and is still in progress. We have looked at the structures of a number if tetrahydroisoquinoline derivatives, a number of differently substituted imines, phenyleacetanilydes, benzanilides and azobenzenes [3] etc. in order to elucidate the influence of "Organic fluorine" in crystal engineering both in the presence and in the absence of strong hydrogen bonding functional groups present within the molecule. A short summary of our observations will be highlighted in the presentation.
Nitrile-Halogen Interactions in Some Bridge-Flipped Isomeric Benzylideneanilines
Authors: Ojala William , Lystad Kendra , Smieja Jonathan , Fermanich Jaclyn , Ojala Charles
Published: November 2015

We designate as "bridge-flipped isomers" those pairs of molecules that differ only in the orientation of a bridge of atoms linking two major molecular fragments: in benzylideneanilines, Ar-CH=N-Ar' vs. Ar-N=CH-Ar'; in phenylhydrazones, Ar-NH-N=CH-Ar' vs. Ar-CH=N-NH-Ar' (Ar = aryl). We use them as a context in which to evaluate the roles of molecular conformation, hydrogen bonding, space-filling requirements, and supramolecular synthons in establishing crystalline isomorphism or non-isomorphism. To examine nitrile-halogen and halogen-halogen interactions in solid isomeric benzylideneanilines, we have determined the structures of 2-cyanobenzylidene-2'-iodoaniline (I), 2-iodobenzylidene-2'-cyanoaniline (II), 2-cyanobenzylidene-2'-bromoaniline (III), 2-cyanobenzylidene-2'-chloroaniline (IV), and 2-chlorobenzylidene-2'-cyanoaniline (V) by single-crystal X-ray diffraction. I/II and IV/V are bridge-flipped isomeric pairs. I, III, and IV are isomorphous; the I/II and IV/V pairs are not. In I, III, and IV, translationally related molecules are linked into chains by C≡N···X contacts; no close X···X contacts occur. Although C≡N···X contacts between translationally related molecules define chains in II similar to those in I, III, and IV, and although II likewise lacks close X···X contacts, the molecular packing arrangements differ (monoclinic for I, III, and IV vs. triclinic for II). V in contrast assumes an orthorhombic structure from which the C≡N···X interaction is absent and which is isomorphous with 2-chlorobenzylidene-2'-chloroaniline (VI), the nitrile group of V exchanged for the aniline-side chlorine of VI, that chlorine atom in VI not involved in a close intermolecular Cl···Cl contact. Although neither C≡N···X nor X···X contacts result in isomorphous bridge-flipped isomers in the cases of I/II and IV/V, the C≡N···X contacts apparently play a major structure-defining role and supersede any potential X···X contacts in I-IV.
Influence of the electrostatic environment on I3-···I3- and related I–M–I···I–M–I interactions
Authors: Esterhuysen Catharine , Groenewald Ferdinand , Elgadi Gamra , Dillen Jan
Published: November 2015

Non-covalent interactions in crystals are notoriously difficult to calculate accurately [1], due to the poor computational description of dispersion, which is often an important component of such interactions. This is particularly true for I3-···I3- interactions, which are observed in crystal structures despite the strong electrostatic repulsion between two negatively charged species [2]. Similarly, related metal-iodides exhibit I–M–I···I–M–I interactions. In an effort to explain this phenomenon a thorough Cambridge Structural Database (CSD) analysis and theoretical study of the triiodide ion, metal-iodides and I···I interactions within dimers of these species in a variety of environments is presented here. Optimisations in the gas phase and in an implicit polarisable continuum solvent model with several different solvents show that there is a significant dependence of the I3-···I3- interaction energy on the dielectric constant. The MP2/cc-pVTZ-pp level of theory comes closest to reproducing the I3- bondlength and the I3-···I3-intermolecular distance averages obtained from the Cambridge Structural Database (CSD). DFT methods are in general not as successful since they do not correctly model dispersion, however, the PBE method used in conjunction with Grimme's D2 dispersion correction [3] yields an interaction energy which is less than 2% from the CCSD/aug-cc-pVTZ-pp// MP2/cc-pVTZ-pp result. The Electrostatic Surface Potential (ESP) of the I3- ion in the gas phase, chloroform, ethanol, water and n-methyl-formamide-mixture can be used as a gauge of the influence of the electrostatic environment on the properties of both the I3- ion and the I3-···I3- interaction, or similarly I-M-I···I-M-I interactions. This information can then be used to extrapolate to obtain a value for the strength of the I···I inter-ion interaction energy in the solid state in a variety of complexes.
Crystallographic Study of a coordination polymer based on Zn2+ion
Authors: De Abreu Heitor , Diniz Renata , De Almeida Filipe
Published: November 2015

Several studies have aimed to better understand coordination polymers, which are structures based on a connection between a metal ion and an organic ligand that extends infinitely, forming a macro-structure1. The interest in this type of structure is mainly due to its properties, such as its pore-forming ability, presenting many potential applications2 like selective separations, catalysis and gas storage. It is interesting to study the structure of coordination polymers to focus in some particular future application. In these way, a coordination polymer was synthetized by simple mixture with isonicotinylhydrazine (INH) and 1,2,4,5-benzenetetracarboxylic acid (BTC) ligands and zinc metallic ion. Yellow single crystals were formed in solution and one was separated, measured and solved by single crystal X-ray diffraction. The crystal-data for the structure were collected using an Oxford GEMINI A-Ultra diffractometer with MoKα radiation (λ = 0.71073 Å) at room temperature and solved using SHELXL-97 program3. The compound crystallized in monoclinic crystalline system in space group P21/c, cell parameters: a=9.2502(6) Å, b= 15.0004(6) Å, c=9.2947(4) Å, β= 108.4590(6), V=1223,35 Å3and Z=4. The final statistical parameters of the structure refinement were R=0.0326, wR=0.0835 and S=1,053. In this compound the BTC and INH ligands are coordinated like a bridge to two zinc ions. The BTC forms chelates by two carboxylate groups and INH coordinates by pyridine ring and by chelate at hydrazide group. This polymer extends in only one direction along a axis forming a 1D network. There is only one metallic zinc ion crystallographically independent on structure, it is in a distorted octahedral geometry with oxygen and nitrogen atoms of ligands and one coordinated water molecule in its coordination sphere. The 1D network formed by coordination polymers stabilizes the crystalline arrangement by hydrogen bonds between carboxylate and hydrazide groups and coordinated water molecules.
Exploring the structural landscape in nia derivatives and their Cd(II) complexes
Authors: Đaković Marijana , Soldin Željka , Petrović Peroković Vesna , Kodrin Ivan , Popović Zora
Published: November 2015

Constant need for design of new materials with desired and pre-determined bulk properties necessitates much improved understanding of competition and balance between non-covalent interactions. In order not to rely on serendipity when targeting synthesis of new solids with pre-determined connectivity and topology, as this offers a path towards the design of materials with pre-determined bulk properties, it is imperative to map out the reliability and robustness of supramolecular synthons. In this contribution, we want to delineate the effect of the counter ion accommodation in the supramolecular assembly on the synthon formation. We opted for positively charged pyridine-based organic molecules that are encoded with two functionalities, caboxamide and carboxylic acid moieties, which both proved as robust and reliable self-complementary reagents, accompanied with one of the three halide counter ions (Cl-, Br-, I-). The study thus focuses on the competition and hierarchy of supramolecular synthons in organic systems of the ligands themselves as well as in the Cd(II)-containing architectures (upon the ligand coordination) depending on the polarizability of the present halide ion. Furthermore, the most prominent intermolecular contacts in the crystal structures will be visualized by Hirshfeld surface analysis and their contributions to the Hirshfeld surface area will be determined. Bader's QTAIM (Quantum Theory of Atoms in Molecules) analysis will be used to characterize the nature and strength of intermolecular interactions based on the DFT calculations started from X-ray determined geometries. The computationally determined data will be compared with the experimental results to get unbiased analysis about the role of specific intermolecular interactions on crystal packing of examined compounds.