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The structure of a protein complex between a bacterial and a human protein solved using data collected at Diamond Light Source (UK) and the ESRF (FRANCE) has revealed the way in which bacteria that cause bacterial meningitis mimic human cells to evade the body’s innate immune system. The study, published in Nature, could lead to the development of new vaccines that give better protection against meningitis B, the strain which accounts for the vast majority of cases of the disease in the UK.
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Prof. Ian Robinson, who holds a joint appointment with University College London (UCL) and Diamond Light Source, has been awarded funding by the Biotechnology and Biological Sciences Research Council (BBSRC) for a 5-year BBSRC ‘Diamond Fellowship'.
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Violerythrin, a blue colored carotenoid, has been investigated by X-ray crystallography and by steady-state and ultrafast time-resolved absorption spectroscopy.
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Seasonal epidemics and worldwide pandemics caused by influenza A viruses are of continuous public health concern. During infection, the viral nonstructural (NS1) protein stimulates phosphoinositide 3-kinase (PI3K) signaling, an essential cell survival pathway commonly mutated in human cancers. A structure of the NS1 effector domain in complex with the p85β inter-SH2 (coiled-coil) domain suggests that NS1 uses the coiled-coil as a structural tether to sterically prevent normal inhibitory ...
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Crystal engineering of nanoporous structures has not yet exploited the heme motif so widely found in proteins. X-ray diffraction (XRD) analysis on Beamline I19 found that metal complexes of a phthalocyanine, a close analog of heme, forms molecular crystals that contain large interconnected voids (8 nm3), defined by a cubic assembly of six phthalocyanines. Rapid ligand exchange at the metal centres is achieved within these phthalocyanine nanoporous crystals (PNCs) by ...
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Porous materials have wide ranging applications in areas such as hydrogen storage, catalysis and drug delivery. In rigid porous materials such as zeolites, the ability of the material to adsorb depends on the fixed size and shape of the pores. Until the mid 1990s most synthetic porous materials were either zeolites and their analogs or activated carbons. The discovery of metal-organic frameworks (MOFs) opened the possibility of more flexible frameworks, where the geometry of the pores can ...
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The Structures of Life
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Molecular layers held together by non-covalent interactions on solid surfaces have gained increasing importance in recent times owing to their diverse commercial and academic applications and the ability to control behaviour by changing the molecular architecture of the adsorbing compounds. High-flux experiments on the powder diffraction beamline I11 at Diamond have enabled very accurate structural characterisation of a particular class of organic compounds, alkyl amides, adsorbed on the ...
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To establish successful infection, a retrovirus must insert DNA replica of its genome into a host cell chromosome. This process is catalysed by integrase (IN), the viral enzyme that synapses ends of viral DNA forming a highly stable nucleoprotein complex, intasome. The structure of full-length IN, either separately or in complex with viral DNA, has been lacking. Furthermore, although clinically useful inhibitors of HIV IN have been developed, their mechanism of action remained speculative. ...
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Researchers from the University of Cambridge have used Diamond Light Source to solve the 3D structure of a protein that plays a major role in hypertension in pre-eclampsia.
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A major programme of research into metal-organic frameworks (MOFs) as materials for hydrogen and fuel gas storage is underway at the University of Nottingham. Safe, efficient hydrogen storage is a pre-condition for powering cars using this clean fuel, which has no carbon emissions at the point of use. In order to understand how our MOFs can store hydrogen, we need to determine their three-dimensional crystal structures. This is often not possible to achieve in-house because the crystals are ...
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DNA repair is found in all branches of life, it is the natural response to an environment which damages DNA. Defects in repair, structure of the archaeal protein XPD provides a model to interpret genetic mutations of the human homologue. These mutations lead to three related diseases: xeroderma pigmentosum (XP), trichothiodystrophy (TTD), and combined XP with Cockayne’s syndrome (XP/CS). The sequence homology allows us to use an orthologue from the organism Sulfolobus sulfataricus which we ...
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Materials with metastable excited states hold great potential for optical data storage applications. Their functionality arises directly from their ability to act as binary switches: if the ground state is taken to signify a ‘0’ and the metastable state a ‘1’, data can be written and re-read using suitable wavelengths of light. However, only a handful of such materials have been reported and little is known about the correlation between their structure and optical properties. As part of an ...
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Ordered protein aggregation is thought to be the cause of several diseases including Alzheimer’s, Huntington’s, Parkinson’s, the prion encephalopathies, and many more. However, the molecular basis of the intermolecular linkage of the underlying protein (Aβ1-42, huntingtin, α-synuclein, and prions) is not known for any of these ‘conformational diseases’ [1]. The SERPIN family of proteins also cause disease when mutations lead to their intracellular aggregation. The process has become known as ...
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We have used the high intensity x-ray beam on beamline I15 to examine the crystal structures of the alkali metals Na and K to above 100 GPa (1 million atmospheres). In Na, we have utilised the low melting temperature near 100 GPa to grow a single crystal of sodium at 108 GPa, and have investigated the complex crystal structure at this pressure using single-crystal diffraction. We confirm that at this pressure sodium is isostructural with the cI16 phase of lithium, and we have refined the ...
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Rho family GTPases are important cellular switches and control a number of physiological functions. Understanding the molecular basis of interaction of these GTPases with their effectors is crucial in understanding their functions in the cell. Here we present the crystal structure of he complex of Rac2 bound to the split pleckstrin homology (spPH) domain of phospholipase C-γ2 (PLCγ2). Based on this structure, we illustrate distinct requirements for PLCγ2 activation by Rac and EGF and ...
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Over the last few years, IR absorption spectroscopy has grown up as a potential analytical method in tissue and cell studies for cancer diagnosis. The application could be twofold: as a tool to assess the presence or absence of malignant cells in biopsies; and as an aid to help pathologists to classify those cells that are suspicious but not diagnostic for cancer. The last application has the problem that in order to assess these cells pathologists would have already dealt with stained ...
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The crystal structure of the high-pressure ζ-form of the explosive CL-20 has been determined using a combination of x-ray single crystal and powder diffraction techniques. Conformational changes in the orientation of the nitro groups of the CL-20 molecule were observed in the γ→ζ transition, such that molecules in the ζ-form adopt the conformation in which all of the nitro groups are exo with respect to the five- and six-membered rings. The level of complexity of this crystal structure ...
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A combined time-resolved synchrotron-based Wide-Angle X-ray Scattering (WAXS) utilising a controlled chemical synthesis apparatus including electrochemical monitoring of the reaction was successfully developed to study the formation and transformation of the redox-reactive ‘green rust’ phases. Iron corrosion in some marine environments and waterlogged soils is known to involve the formation of dark olive-green compounds called green rusts (GR) which transform quickly into the usual brown ...
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Rho proteins are small GTPases that function to regulate cell motility, polarity, adhesion, cytoskeletal organisation, proliferation and apoptosis. Two distinct families of Rho guanine nucleotide exchange factors (GEFs), the Dbl homology (DH) and DOCK proteins, activate Rho GTPases through the exchange of GDP for GTP. In humans, DOCK proteins are organised into four subfamilies, characterised by their differing specificities for Rac and Cdc42, regulatory domains and associated subunits. All ...
