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Jul 2007
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Abstract: High-resolution inelastic x-ray scattering (IXS) was carried out in the filled-skutterudites ROs4Sb12 (R = La, Pr, Nd, Sm). Low-energy rare-earth modes were found in these compounds. They show significant rare-earth dependence, suggesting a correlation with lanthanide contraction. We discuss the relation between the present IXS measurements and reported other experiments.
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Jan 2010
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Mar 2009
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Abstract: Vacuolar?type ATPases (V?ATPases) exist in various cellular membranes of many organisms to regulate physiological processes by controlling the acidic environment. Here, we have determined the crystal structure of the A3B3 subcomplex of V?ATPase at 2.8 Å resolution. The overall construction of the A3B3 subcomplex is significantly different from that of the ?3?3 sub?domain in FoF1?ATP synthase, because of the presence of a protruding ‘bulge’ domain feature in the catalytic A subunits. The A3B3 subcomplex structure provides the first molecular insight at the catalytic and non?catalytic interfaces, which was not possible in the structures of the separate subunits alone. Specifically, in the non?catalytic interface, the B subunit seems to be incapable of binding ATP, which is a marked difference from the situation indicated by the structure of the FoF1?ATP synthase. In the catalytic interface, our mutational analysis, on the basis of the A3B3 structure, has highlighted the presence of a cluster composed of key hydrophobic residues, which are essential for ATP hydrolysis by V?ATPases.
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Nov 2009
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Abstract: The Mapkap kinases 2 and 3 (MK2 and MK3) have been implicated in intracellular signaling pathways leading to the production of the pro-inflammatory cytokine tumor necrosis factor alpha. MK2 has been pursued by the biopharmaceutical industry for many years for the development of a small molecule anti-inflammatory treatment and drug-like inhibitors have been described. The development of some of these compounds, however, has been slowed by the absence of a high-resolution crystal structure of MK2. Herein we present a high-resolution (1.9 angstrom) crystal structure of the highly homologous MK3 in complex with a pharmaceutical lead compound. While all of the canonical features of Ser/Thr kinases in general and MK2 in particular are recapitulated in MK3, the detailed analysis of the binding interaction of the drug-like ligand within the adenine binding pocket allows relevant conclusions to be drawn for the further design of potent and selective drug candidates.
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Jan 2010
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Open Access
Abstract: A molecular understanding of the unique aspects of dietary fructose metabolism may be the key to understanding and controlling the current epidemic of fructose-related obesity, diabetes and related adverse metabolic states in Western populations. Fructose catabolism is initiated by its phosphorylation to fructose 1-phosphate, which is performed by ketohexokinase (KHK). Here, the crystal structures of the two alternatively spliced isoforms of human ketohexokinase, hepatic KHK-C and the peripheral isoform KHK-A, and of the ternary complex of KHK-A with the substrate fructose and AMP-PNP are reported. The structure of the KHK-A ternary complex revealed an active site with both the substrate fructose and the ATP analogue in positions ready for phosphorylation following a reaction mechanism similar to that of the pfkB family of carbohydrate kinases. Hepatic KHK deficiency causes the benign disorder essential fructosuria. The effects of the disease-causing mutations (Gly40Arg and Ala43Thr) have been modelled in the context of the KHK structure.
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Mar 2009
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Abstract: The misfolding of proteins and peptides can lead to fibrillar aggregates which are often termed amyloid fibrils. These are characterized by a cross-beta structure, with -strands and polypeptide backbones running perpendicular to the fibril axis, which is coincident with the hydrogen bonding direction. Several types of amyloid fibrils have been shown by high resolution electron microscopy to comprise assemblies of individual twisted -sheets,2-5 of which there are two typesstapes or ribbons. The two are distinguished by the presence or absence of a hollow core in the fibril. The twist arises from packing constraints of the side groups of the residues within the beta-Strands.
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Oct 2008
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Abstract: Energy-dispersive X-ray absorption spectroscopy is an increasingly powerful tool for the investigation of kinetic processes in chemical systems as an element-specific local structure and electronic-state probe. Advances in synchrotron radiation sources and detector technology are pushing the time resolution of the method to ever shorter periods, currently milliseconds to microseconds, while also providing a concomitant improvement in data quality that now makes feasible the identification of structural and electronic motifs characteristic of intermediate states in chemical processes. To maximize the value of the newly available high-quality time-resolved data, techniques for consistent data normalization and structural component analysis have been developed and here are illustrated in a model study of the electron-transfer reaction between [IrCl6]2- with [Co(CN)5]3-.
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Aug 2005
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Abstract: A new high-pressure phase of pure nitric acid (HNO(3)) has been characterised at 1.6 GPa at room temperature by high-pressure neutron powder and X-ray single-crystal diffraction techniques. This is the first crystalline phase obtained upon compression of liquid nitric acid at room temperature and appears to be the stable phase up to pressures of at least 4 GPa. The crystal structure of this new phase shows some similarities to that of the low-temperature phase of nitric acid at ambient pressure, which has been redetermined as part of this study. Both structures share a herringbone packing of hydrogen-bonded molecular catemers, although the presence of disorder within the hydrogen bonds within one of the catemers of the low-temperature phase makes its structure comparatively more complex.
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Jan 2010
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Abstract: Time resolved energy dispersive X-ray absorption spectroscopy has been used to follow the structural evolution of the inner-sphere electron transfer reaction between [IrCl6]2? and [Co(CN)5]3?, and to characterise the local structure of the iridium metal centre in the bridged activated complex formed during the reaction.
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Sep 2005
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