I03-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Luís A. R.
Carvalho
,
Vanessa T.
Almeida
,
Jose A.
Brito
,
Kenneth M.
Lum
,
Tânia F.
Oliveira
,
Rita C.
Guedes
,
Lídia M.
Gonçalves
,
Susana D.
Lucas
,
Benjamin F.
Cravatt
,
Margarida
Archer
,
Rui
Moreira
Diamond Proposal Number(s):
[20161]
Abstract: 3-Oxo-β-sultams are four-membered ring ambident electrophiles that can react with nucleophiles either at the carbonyl carbon or at the sulfonyl sulfur atoms, and that have been reported to inhibit serine hydrolases via acylation of the active-site serine residue. We have developed a panel of 3-oxo-β-sultam inhibitors and show, through crystallographic data, that they are regioselective sulfonylating electrophiles, covalently binding to the catalytic serine of human and porcine elastases through the sulfur atom. Application of 3-oxo-β-sultam-derived activity-based probes in a human proteome revealed their potential to label disease-related serine hydrolases and proteasome subunits. Activity-based protein profiling applications of 3-oxo-β-sultams should open up new opportunities to investigate these classes of enzymes in complex proteomes and expand the toolbox of available sulfur-based covalent protein modifiers in chemical biology.
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Mar 2020
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B21-High Throughput SAXS
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Kate
Mcaulay
,
Pedro Agís
Ucha
,
Han
Wang
,
Ana M.
Fuentes-caparros
,
Lisa
Thomson
,
Osama
Maklad
,
Nikul
Khunti
,
Nathan
Cowieson
,
Matthew
Wallace
,
Honggang
Cui
,
Robert J.
Poole
,
Annela
Seddon
,
Dave J.
Adams
Diamond Proposal Number(s):
[19847]
Open Access
Abstract: The micellar aggregates formed at high pH for dipeptide-based gelators can be varied by using different alkali metal salts to prepare the solutions. The nature of the micellar aggregates directly affects the properties of the resulting gels.
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Mar 2020
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I05-ARPES
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Diamond Proposal Number(s):
[15822]
Open Access
Abstract: Van der Waals materials offer unprecedented control of electronic properties via stacking of different types of two-dimensional materials. A fascinating frontier, largely unexplored, is the stacking of strongly correlated phases of matter. We study 4Hb-TaS2, which naturally realizes an alternating stacking of 1T-TaS2 and 1H-TaS2 structures. The former is a well-known Mott insulator, which has recently been proposed to host a gapless spin-liquid ground state. The latter is a superconductor known to also host a competing charge density wave state. This raises the question of how these two components affect each other when stacked together. We find a superconductor with a Tc of 2.7 Kelvin and anomalous properties, of which the most notable one is a signature of time-reversal symmetry breaking, abruptly appearing at the superconducting transition. This observation is consistent with a chiral superconducting state.
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Mar 2020
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Pedram
Mehrabi
,
Henrike
Mueller-werkmeister
,
Jan-philipp
Leimkohl
,
Hendrik
Schikora
,
Jelena
Ninkovic
,
Silvia
Krivokuca
,
Ladislav
Andriček
,
Sascha W.
Epp
,
Darren A.
Sherrell
,
Robin L.
Owen
,
Arwen R.
Pearson
,
Friedjof
Tellkamp
,
Eike
Schulz
,
R. J. Dwayne
Miller
Open Access
Abstract: Serial synchrotron crystallography (SSX) is an emerging technique for static and time-resolved protein structure determination. Using specifically patterned silicon chips for sample delivery, the `hit-and-return' (HARE) protocol allows for efficient time-resolved data collection. The specific pattern of the crystal wells in the HARE chip provides direct access to many discrete time points. HARE chips allow for optical excitation as well as on-chip mixing for reaction initiation, making a large number of protein systems amenable to time-resolved studies. Loading of protein microcrystals onto the HARE chip is streamlined by a novel vacuum loading platform that allows fine-tuning of suction strength while maintaining a humid environment to prevent crystal dehydration. To enable the widespread use of time-resolved serial synchrotron crystallography (TR-SSX), detailed technical descriptions of a set of accessories that facilitate TR-SSX workflows are provided.
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Mar 2020
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E02-JEM ARM 300CF
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Diamond Proposal Number(s):
[20431, 22317]
Abstract: We report the application of focused probe ptychography using binary 4D datasets obtained using scanning transmission electron microscopy (STEM). Modern fast pixelated detectors have enabled imaging of individual convergent beam electron diffraction patterns in a STEM raster scan at frame rates in the range of 1000–8000 Hz using conventional counting modes. Changing the bit depth of a counting detector, such that only values of 0 or 1 can be recorded at each pixel, allows one to decrease the dwell time and increase the frame rate to 12.5 kHz, reducing the electron exposure of the sample for a given beam current. Atomically resolved phase contrast of an aluminosilicate zeolite (ZSM-5) is observed from sparse diffraction patterns with isolated individual electrons, demonstrating the potential of binary ptychography as a low-dose 4D STEM technique.
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Mar 2020
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I11-High Resolution Powder Diffraction
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Diamond Proposal Number(s):
[9282]
Abstract: A porous organic cage crystal, α-CC2, shows unexpected adsorption of sulphur hexafluoride (SF6) in its cage cavities, which are formally occluded even to the smallest diatomic gas, H2, according to a pore analysis of the static crystal structure. In situ powder X-ray diffraction (PXRD) experiments provide unequivocal evidence for the presence of (SF6) inside the ‘occluded’ cage voids, pointing to a mechanism of dynamic flexibility of the system. By combining PXRD results with molecular dynamics simulations, we build a molecular level picture of the cooperative porosity in α-CC2 that facilitates the passage of (SF6) into the cage voids.
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Mar 2020
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I03-Macromolecular Crystallography
I24-Microfocus Macromolecular Crystallography
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Diamond Proposal Number(s):
[14744]
Open Access
Abstract: The transmembrane protein OTK plays an essential role in plexin and Wnt signaling during Drosophila development. We have determined a crystal structure of the last three domains of the OTK ectodomain and found that OTK shows high conformational flexibility resulting from mobility at the interdomain interfaces. We failed to detect direct binding between Drosophila Plexin A (PlexA) and OTK, which was suggested previously. We found that, instead of PlexA, OTK directly binds semaphorin 1a. Our binding analyses further revealed that glycosaminoglycans, heparin and heparan sulfate, are ligands for OTK and thus may play a role in the Sema1a-PlexA axon guidance system.
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Mar 2020
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I11-High Resolution Powder Diffraction
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Abstract: Light weight and cheap electrolytes with fast multi-valent ion conductivity can pave the way for future high-energy density solid-state batteries, beyond the lithium-ion battery. Here we present the mechanism of Mg-ion conductivity of monoammine magnesium borohydride, Mg(BH4)2·NH3. Density functional theory calculations (DFT) reveal that the neutral molecule (NH3) in Mg(BH4)2·NH3 is exchanged between the lattice and interstitial Mg2+ facilitated by a highly flexible structure, mainly owing to a network of di-hydrogen bonds, N–Hδ+⋯−δH–B and the versatile coordination of the BH4− ligand. DFT shows that di-hydrogen bonds in inorganic matter and hydrogen bonds in bio-materials have similar bond strengths and bond lengths. As a result of the high structural flexibiliy, the Mg-ion conductivity is dramatically improved at moderate temperature, e.g. σ(Mg2+) = 3.3 × 10−4 S cm−1 at T = 80 °C for Mg(BH4)2·NH3, which is approximately 8 orders of magnitude higher than that of Mg(BH4)2. Our results may inspire a new approach for the design and discovery of unprecedented multivalent ion conductors.
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Mar 2020
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I06-Nanoscience
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M.
Wang
,
C.
Andrews
,
S.
Reimers
,
O. J.
Amin
,
P.
Wadley
,
R. P.
Campion
,
S. F.
Poole
,
J.
Felton
,
K. W.
Edmonds
,
B. L.
Gallagher
,
A. W.
Rushforth
,
O.
Makarovsky
,
K.
Gas
,
M.
Sawicki
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D.
Kriegner
,
J.
Zubáč
,
K.
Olejník
,
V.
Novák
,
T.
Jungwirth
,
M.
Shahrokhvand
,
U.
Zeitler
,
S. S.
Dhesi
,
F.
Maccherozzi
Diamond Proposal Number(s):
[11846, 20793]
Abstract: We report magnetic-field-induced rotation of the antiferromagnetic Néel vector in epitaxial CuMnAs thin films. First, using soft x-ray magnetic linear dichroism spectroscopy as well as magnetometry, we demonstrate spin-flop switching and continuous spin reorientation in films with uniaxial and biaxial magnetic anisotropies, respectively, for applied magnetic fields of the order of 2 T. The remnant antiferromagnetic domain configurations are determined using x-ray photoemission electron microscopy. Next, we show that the Néel vector reorientations are manifested in the longitudinal and transverse anisotropic magnetoresistance. Dependencies of the electrical resistance on the orientation of the Néel vector with respect to both the electrical current direction and the crystal symmetry are identified, including a weak fourth-order term evident at high magnetic fields. The results provide characterization of key parameters including the anisotropic magnetoresistance coefficients, magnetocrystalline anisotropy, and spin-flop field in epitaxial films of tetragonal CuMnAs, a candidate material for antiferromagnetic spintronics.
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Mar 2020
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I03-Macromolecular Crystallography
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Olivia J. S.
Macleod
,
Jean-mathieu
Bart
,
Paula
Macgregor
,
Lori
Peacock
,
Nicholas J.
Savill
,
Svenja
Hester
,
Sophie
Ravel
,
Jack D.
Sunter
,
Camilla
Trevor
,
Steven
Rust
,
Tristan J.
Vaughan
,
Ralph
Minter
,
Shabaz
Mohammed
,
Wendy
Gibson
,
Martin C.
Taylor
,
Matthew
Higgins
,
Mark
Carrington
Diamond Proposal Number(s):
[18069]
Open Access
Abstract: Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator.
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Mar 2020
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