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14,322 items found (0 items not approved), displaying 21 to 30.[First/Prev] 1, 2, 3, 4, 5, 6, 7, 8 [Next/Last]

Instruments / Technical Area	Publication Details	Published
I04-1-Macromolecular Crystallography (fixed wavelength)	1.25 Å resolution structure of an RNA 20-mer that binds to the TREX2 complex Eugene Valkov , Murray Stewart Acta Crystallographica Section F Structural Biology Communications 71, 1318 - 1321 DOI: 10.1107/S2053230X1501643X PMID: 26457524 Open Access Show Abstract ▼ Abstract: The 1.25 Å resolution H32:R crystal structure of a 20 nt ribonucleotide that binds to the TREX-2 complex with high affinity shows a double-stranded RNA duplex arranged along a crystallographic 31 axis in which the antiparallel chains overlap by 18 nucleotides and are related by a crystallographic twofold axis. The duplex shows C–A, U–U and C–C noncanonical base pairings together with canonical Watson–Crick A–U and G–C pairs and a G–U wobble.	Oct 2015
I04-1-Macromolecular Crystallography (fixed wavelength)	1.8 Å resolution crystal structure of the carbapenem intrinsic resistance protein CarF Evelyn M. Tichy , Steven W. Hardwick , Ben F. Luisi , George P. C. Salmond Acta Crystallographica Section D Structural Biology 73, 549 - 556 DOI: 10.1107/S2059798317002236 Show Abstract ▼ Abstract: The natural production of the β-lactam antibiotic carbapenem in bacteria involves a group of enzymes that form a synthetic pathway as well as proteins that protect the cell from self-intoxification by the products. Here, the crystal structure of CarF, one of the two proteins that confer resistance to synthesis of the antibiotic in the host organism, is reported. The CarF fold places it within a widely occurring structural family, indicating an ancient structural origin from which the resistance function has been derived.	Jul 2017
I04-1-Macromolecular Crystallography (fixed wavelength)	10-Iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A Hannes Falke , Apirat Chaikuad , Anja Becker , Nadã¨ge Loaec , Olivier Lozach , Samira Abu Jhaisha , Walter Becker , Peter G. Jones , Lutz Preu , Knut Baumann , Stefan Knapp , Laurent Meijer , Conrad Kunick Journal Of Medicinal Chemistry 58 (7) DOI: 10.1021/jm501994d PMID: 25730262 Diamond Proposal Number(s): [8421, 10619] Open Access Show Abstract ▼ Abstract: The protein kinase DYRK1A has been suggested to act as one of the intracellular regulators contributing to neurological alterations found in individuals with Down syndrome. For an assessment of the role of DYRK1A, selective synthetic inhibitors are valuable pharmacological tools. However, the DYRK1A inhibitors described in the literature so far either are not sufficiently selective or have not been tested against closely related kinases from the DYRK and the CLK protein kinase families. The aim of this study was the identification of DYRK1A inhibitors exhibiting selectivity versus the structurally and functionally closely related DYRK and CLK isoforms. Structure modification of the screening hit 11H-indolo[3,2-c]quinoline-6-carboxylic acid revealed structure–activity relationships for kinase inhibition and enabled the design of 10-iodo-substituted derivatives as very potent DYRK1A inhibitors with considerable selectivity against CLKs. X-ray structure determination of three 11H-indolo[3,2-c]quinoline-6-carboxylic acids cocrystallized with DYRK1A confirmed the predicted binding mode within the ATP binding site.	Mar 2015
I13-2-Diamond Manchester Imaging	11β-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy C. G. Fenton , C. L. Doig , S. Fareed , A. Naylor , A. P. Morrell , O. Addison , C. Wehmeyer , C. D. Buckley , M. S. Cooper , G. G. Lavery , K. Raza , R. S. Hardy Arthritis Research & Therapy 21 DOI: 10.1186/s13075-019-1972-1 Diamond Proposal Number(s): [16654] Open Access Show Abstract ▼ Abstract: Background: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11β-HSD1 to GIOP. Methods: Wild type (WT) and 11β-HSD1 knockout (KO) mice were treated with corticosterone (100 μg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11β-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. Conclusions: This study demonstrates that 11β-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11β-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids.	Aug 2019
I02-Macromolecular Crystallography	12-Fold symmetry of the putative portal protein from the Thermus thermophilus bacteriophage G20C determined by X-ray analysis Lowri S. Williams , Vladimir Levdikov , Leonid Minakhin , Konstantin Severinov , Alfred A. Antson Acta Crystallographica Section F Structural Biology And Crystallization Communications 69 DOI: 10.1107/S174430911302486X PMID: 24192358 Open Access Show Abstract ▼ Abstract: In tailed bacteriophages and several animal viruses, the portal protein forms the gateway through which viral DNA is translocated into the head structure during viral particle assembly. In the mature virion the portal protein exists as a dodecamer, while recombinant portal proteins from several phages, including SPP1 and CNPH82, have been shown to form 13-subunit assemblies. A putative portal protein from the thermostable bacteriophage G20C has been cloned, overexpressed and purified. Crystals of the protein diffracted to 2.1 Å resolution and belonged to space group P4212, with unit-cell parameters a = b = 155.3, c = 115.4 Å. The unit-cell content and self-rotation function calculations indicate that the protein forms a circular 12-subunit assembly.	Nov 2013
B16-Test Beamline Detectors Diagnostics	12th international conference on synchrotron radiation instrumentation – SRI2015 Christopher Bloomer , Guenther Rehm , Igor Dolbnya AIP Conference Proceedings DOI: 10.1063/1.4952845 Open Access Show Abstract ▼ Abstract: Maintaining the stability of the X-ray beam relative to the sample point is of paramount importance for beamlines and users wanting to perform cutting-edge experiments. The ability to detect, and subsequently compensate for, variations in X-ray beam position with effective diagnostics has multiple benefits: a reduction in commissioning and start-up time, less ‘down-time’, and an improvement in the quality of acquired data. At Diamond Light Source a methodical evaluation of a selection of monochromatic X-ray Beam Position Monitors (XBPMs), using a range of position detection techniques, and from a range of suppliers, was carried out. The results of these experiments are presented, showing the measured RMS noise on the position measurement of each device for a given flux, energy, beam size, and bandwidth. A discussion of the benefits and drawbacks of each of the various devices and techniques is also included.	Jul 2016
I04-Macromolecular Crystallography	13 C-Carbamylation as a mechanistic probe for the inhibition of class D β-lactamases by avibactam and halide ions Christopher T. Lohans , David Y. Wang , Christian Jorgensen , Samuel T. Cahill , Ian J. Clifton , Michael A. Mcdonough , Henry P. Oswin , James Spencer , Carmen Domene , Timothy D. W. Claridge , Jurgen Brem , Christopher J. Schofield Organic & Biomolecular Chemistry 6 DOI: 10.1039/C7OB01514C Diamond Proposal Number(s): [12346] Open Access Show Abstract ▼ Abstract: The class D (OXA) serine β-lactamases are a major cause of resistance to β-lactam antibiotics. The class D enzymes are unique amongst β-lactamases because they have a carbamylated lysine that acts as a general acid/base in catalysis. Previous crystallographic studies led to the proposal that β-lactamase inhibitor avibactam targets OXA enzymes in part by promoting decarbamylation. Similarly, halide ions are proposed to inhibit OXA enzymes via decarbamylation. NMR analyses, in which the carbamylated lysines of OXA-10, -23 and -48 were 13C-labelled, indicate that reaction with avibactam does not ablate lysine carbamylation in solution. While halide ions did not decarbamylate the 13C-labelled OXA enzymes in the absence of substrate or inhibitor, avibactam-treated OXA enzymes were susceptible to decarbamylation mediated by halide ions, suggesting halide ions may inhibit OXA enzymes by promoting decarbamylation of acyl-enzyme complex. Crystal structures of the OXA-10 avibactam complex were obtained with bromide, iodide, and sodium ions bound between Trp-154 and Lys-70. Structures were also obtained wherein bromide and iodide ions occupy the position expected for the ‘hydrolytic water’ molecule. In contrast with some solution studies, Lys-70 was decarbamylated in these structures. These results reveal clear differences between crystallographic and solution studies on the interaction of class D β-lactamases with avibactam and halides, and demonstrate the utility of 13C-NMR for studying lysine carbamylation in solution.	Jun 2017
I07-Surface & interface diffraction	13.9% efficiency ternary nonfullerene solar cells featuring low-structural order Baocai Du , Renyong Geng , Wei Li , Donghui Li , Yuchao Mao , Mengxue Chen , Xue Zhang , Joel A. Smith , Rachel C. Kilbride , Mary E. O'Kane , Dan Liu , David G. Lidzey , Weihua Tang , Tao Wang Acs Energy Letters DOI: 10.1021/acsenergylett.9b01630 Diamond Proposal Number(s): [22651] Show Abstract ▼ Abstract: The insufficient phase separation between polymer donors and non-fullerene acceptors (NFAs) featuring with low-structural orders disrupts efficient charge transport and increases charge recombination, consequently limits the maximum achievable power conversion efficiency (PCE) of organic solar cells (OSCs). Herein, an NFA IT-M has been added as the third component into the PBDB-T:m-INPOIC OSCs, and is shown to effectively tune the phase separation between donor and acceptor molecules, although all components in the ternary system exhibit low degrees of structural orders. The incorporation of 10 wt% IT-M into a PBDB-T:m-INPOIC binary host blend appreciably increases the length scale of phase separation, creating continuous pathways which increase and balance charge transport. This leads to an enhanced photovoltaic performance from 12.8% in the binary cell to 13.9% for the ternary cell with simultaneously improved open-circuit voltage, short-circuit current and fill factor. This work highlights the beneficial role of ternary components in controlling the morphology of the active layer for high performance OSCs.	Sep 2019
I03-Macromolecular Crystallography	14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface Tobias Karlberg , Peter Hornyak , Ana Filipa Pinto , Stefina Milanova , Mahsa Ebrahimi , Mikael Lindberg , Nikolai Püllen , Axel Nordström , Elinor Löverli , Rémi Caraballo , Emily V. Wong , Katja Näreoja , Ann-Gerd Thorsell , Mikael Elofsson , Enrique M. De La Cruz , Camilla Björkegren , Herwig Schüler Nature Communications 9 DOI: 10.1038/s41467-018-06194-1 Diamond Proposal Number(s): [11265, 15806] Open Access Show Abstract ▼ Abstract: Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3β:ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.	Sep 2018
I24-Microfocus Macromolecular Crystallography	14-3-3 proteins interact with a hybrid prenyl-phosphorylation motif to inhibit G proteins Philippe Riou , Svend Kjær , Ritu Garg , Andy Purkiss , Roger George , Robert J. Cain , Ganka Bineva , Nicolas Reymond , Brad Mccoll , Andrew Thompson , Nicola O'Reilly , Neil Mcdonald , Peter J. Parker , Anne J. Ridley Cell 153 (3), 640 - 653 DOI: 10.1016/j.cell.2013.03.044 PMID: 23622247 Diamond Proposal Number(s): [8015] Open Access Show Abstract ▼ Abstract: Signaling through G proteins normally involves conformational switching between GTP- and GDP-bound states. Several Rho GTPases are also regulated by RhoGDI binding and sequestering in the cytosol. Rnd proteins are atypical constitutively GTP-bound Rho proteins, whose regulation remains elusive. Here, we report a high-affinity 14-3-3-binding site at the C terminus of Rnd3 consisting of both the Cys241-farnesyl moiety and a Rho-associated coiled coil containing protein kinase (ROCK)-dependent Ser240 phosphorylation site. 14-3-3 binding to Rnd3 also involves phosphorylation of Ser218 by ROCK and/or Ser210 by protein kinase C (PKC). The crystal structure of a phosphorylated, farnesylated Rnd3 peptide with 14-3-3 reveals a hydrophobic groove in 14-3-3 proteins accommodating the farnesyl moiety. Functionally, 14-3-3 inhibits Rnd3-induced cell rounding by translocating it from the plasma membrane to the cytosol. Rnd1, Rnd2, and geranylgeranylated Rap1A interact similarly with 14-3-3. In contrast to the canonical GTP/GDP switch that regulates most Ras superfamily members, our results reveal an unprecedented mechanism for G protein inhibition by 14-3-3 proteins.	Apr 2013

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