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Ferentinos E.,National and Kapodistrian University of Athens | Tsoupras A.B.,National and Kapodistrian University of Athens | Roulia M.,National and Kapodistrian University of Athens | Chatziefthimiou S.D.,EMBL Hamburg | And 2 more authors.
Inorganica Chimica Acta | Year: 2011

The Zn[(OPPh2)(SePPh2)N]2 complex was prepared by a metathetical reaction between a Zn(II) salt and the deprotonated form of the dichalcogenoimidodiphosphinato ligand [(OPPh2)(SePPh 2)N]-. X-ray crystallography revealed a pseudo-tetrahedral MO2Se2 coordination sphere, owed to the asymmetric (O,Se) nature of the chelating ligand. A comparison between the structural features of the M[(OPPh2)(SePPh2)N]2 complexes, M = Co, Ni, Zn, shows that the three complexes are isomorphous. The IR and 31P NMR properties of Zn[(OPPh2)(SePPh2)N] 2 are analyzed in the framework of its crystallographic structure, and are compared with data on similar systems. The above three complexes, along with the (OPPh2)(SePPh2)NH ligand and SeO2, are investigated as inhibitors of the Platelet Activating Factor (PAF) and thrombin activities. The paramagnetic M[(OPPh2)(SePPh2)N] 2 complexes, M = Co, Ni, exhibit an approximately 65-fold increased activity, compared to diamagnetic Zn[(OPPh2)(SePPh 2)N]2, in both the PAF- and the thrombin-induced aggregation of washed rabbit platelets (WRP). The above three complexes show a comparable significant inhibitory activity in the PAF-induced aggregation of rabbit platelet rich plasma (RPR). Remarkably, SeO2, a form of Se present in blood, exhibits a very strong and selective inhibitory activity towards the PAF-induced aggregation of WPR. Our studies extend the dataset of metal complexes investigated as inhibitors of PAF and thrombin. © 2011 Elsevier B.V. All rights reserved. Source


Ghasparian A.,University of Zurich | Riedel T.,University of Zurich | Koomullil J.,University of Zurich | Moehle K.,University of Zurich | And 9 more authors.
ChemBioChem | Year: 2011

Engineered nanoparticles have been designed based on the self-assembling properties of synthetic coiled-coil lipopeptide building blocks. The presence of an isoleucine zipper within the lipopeptide together with the aggregating effects of an N-terminal lipid drives formation of 20-25 nm nanoparticles in solution. Biophysical studies support a model in which the lipid is buried in the centre of the nanoparticle, with 20-30 trimeric helical coiled-coil bundles radiating out into solution. A promiscuous T-helper epitope and a synthetic B-cell epitope mimetic derived from the circumsporozoite protein of Plasmodium falciparum have been linked to each lipopeptide chain, with the result that 60-90 copies of each antigen are displayed over the surface of the nanoparticle. These nanoparticles elicit strong humoral immune responses in mice and rabbits, including antibodies able to cross-react with the parasite, thereby, supporting the potential value of this delivery system in synthetic vaccine design. Viral protection: Synthetic virus-like particles (SVLPs) are produced from self-assembling coiled-coil lipopeptide building blocks (see figure). SVLPs allow multivalent display of B-cell epitope mimetics, are highly immunogenic, and can be used to elicit strong epitope- and pathogen-specific humoral immune responses without the use of adjuvants. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


Tamura H.,Max Planck Institute For Terrestrische Mikrobiologie | Tamura H.,Research Institute for Biological science RIBS Okayama | Salomone-Stagni M.,EMBL Hamburg | Fujishiro T.,Max Planck Institute For Terrestrische Mikrobiologie | And 6 more authors.
Angewandte Chemie - International Edition | Year: 2013

Inhibition mechanism: Isocyanides strongly inhibit [Fe]-hydrogenase. X-ray crystallography and X-ray absorption spectroscopy revealed that the isocyanide binds to the trans position, versus the acyl carbon of the Fe center, and is covalently bound to the pyridinol hydroxy oxygen. These results also indicated that the hydroxy group is essential for H2 activation. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source


List F.,EMBL Hamburg | List F.,University of Regensburg | Vega M.C.,EMBL Hamburg | Vega M.C.,CSIC - Biological Research Center | And 4 more authors.
Chemistry and Biology | Year: 2012

Nitrogen is incorporated into various metabolites by multifunctional glutamine amidotransferases via reactive ammonia generated by glutaminase hydrolysis of glutamine. Although this process is generally tightly regulated by subsequent synthase activity, little is known about how the glutaminase is inhibited in the absence of an activating signal. Here, we use imidazoleglycerolphosphate synthase as a model to investigate the mechanism of glutaminase regulation. A structure of the bienzyme-glutamine complex reveals that the glutaminase active site is in a catalysis-competent conformation but the ammonia pathway toward the synthase active site is blocked. Mutation of two residues blocking the pathway leads to a complete uncoupling of the two reactions and to a 2800-fold amplification of glutaminase activity. Our data advance the understanding of coupling enzymatic activities in glutamine amidotransferases and raise hypotheses of the underlying molecular mechanism. © 2012 Elsevier Ltd. Source


Blanchet C.E.,EMBL Hamburg | Zozulya A.V.,EMBL Hamburg | Kikhney A.G.,EMBL Hamburg | Kikhney A.G.,German Electron Synchrotron | And 9 more authors.
Journal of Applied Crystallography | Year: 2012

A setup is presented for automated high-throughput measurements of small-angle X-ray scattering (SAXS) from macromolecular solutions on the bending-magnet beamline X33 of EMBL at the storage ring DORIS-III (DESY, Hamburg). A new multi-cell compartment allows for rapid switching between in-vacuum and in-air operation, for digital camera assisted control of cell filling and for colour sample illumination. The beamline is equipped with a Pilatus 1 M-W pixel detector for SAXS and a Pilatus 300 k-W for wide-angle scattering (WAXS), and results from the use of the Pilatus detectors for scattering studies are reported. The setup provides a broad resolution range from 100 to 0.36 nm without the necessity of changing the sample-to-detector distance. A new optimized robotic sample changer is installed, permitting rapid and reliable automated sample loading and cell cleaning with a required sample volume of 40 l. All the devices are fully integrated into the beamline control software system, ensuring fully automated and user-friendly operation (attended, unattended and remote) with a throughput of up to 15 measurements per hour. © 2012 International Union of Crystallography Printed in Singapore-all rights reserved. Source

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