Solution structure of the Legionella pneumophila Mip-rapamycin complex

<p>Abstract</p> <p>Background</p> <p><it>Legionella pneumphila </it>is the causative agent of Legionnaires' disease. A major virulence factor of the pathogen is the homodimeric surface protein Mip. It shows peptidyl-prolyl cis/trans isomerase activty and is a receptor of FK506 and rapamycin, which both inhibit its enzymatic function. Insight into the binding process may be used for the design of novel Mip inhibitors as potential drugs against Legionnaires' disease.</p> <p>Results</p> <p>We have solved the solution structure of free Mip^77–213and the Mip^77–213-rapamycin complex by NMR spectroscopy. Mip^77–213showed the typical FKBP-fold and only minor rearrangements upon binding of rapamycin. Apart from the configuration of a flexible hairpin loop, which is partly stabilized upon binding, the solution structure confirms the crystal structure. Comparisons to the structures of free FKBP12 and the FKBP12-rapamycin complex suggested an identical binding mode for both proteins.</p> <p>Conclusion</p> <p>The structural similarity of the Mip-rapamycin and FKBP12-rapamycin complexes suggests that FKBP12 ligands may be promising starting points for the design of novel Mip inhibitors. The search for a novel drug against Legionnaires' disease may therefore benefit from the large variety of known FKBP12 inhibitors.</p

Decoupling Charge Transport and Electroluminescence in a High Mobility Polymer Semiconductor.

Fluorescence enhancement of a high-mobility polymer semiconductor is achieved via energy transfer to a higher fluorescence quantum yield squaraine dye molecule on 50 ps timescales. In organic light-emitting diodes, an order of magnitude enhancement of the external quantum efficiency is observed without reduction in the charge-carrier mobility resulting in radiances of up to 5 W str(-1) m(-2) at 800 nm.We gratefully acknowledge funding from the Engineering and Physical Sciences Research Council (EPSRC) through a programme grant EP/M005143/1. We would like to thank the Doctoral Training Centre in Plastic Electronics EP/G037515/1. K. B. acknowledges financial support by the Deutsche Forschungsgemeinschaft (BR-4869/1-1). The group at Würzburg would like to acknowledge support from the Deutsche Forschungsgemeinschaft (DFG Research Unit FOR 1809) and from the SolTech Initiative of the Bavarian State Ministry of Science, Research and the Arts. D. H. and K.B. would like to thank Dr. Jiři Novak and Jakub Rozbořil (Central European Institute of Technology, Masaryk University, Czech Republic) and Dr. Tom Arnold (Diamond Light Source, Didcot, UK) for assistance during the synchrotron experiment and Diamond Light Source, Didcot, UK for financial support

Cooperative enhancement versus additivity of two-photon-absorption cross sections in linear and branched squaraine superchromophores

The linear and nonlinear optical properties of a series of oligomeric squaraine dyes were investigated by one-photon absorption spectroscopy (1PA) and two-photon absorption (2PA) induced fluorescence spectroscopy. The superchromophores are based on two indolenine squaraine dyes with transoid (SQA) and cisoid configuration (SQB). Using these monomers, linear dimers and trimers as well as star-shaped trimers and hexamers with benzene or triphenylamine cores were synthesised and investigated. The red-shifted and intensified 1PA spectra of all superchromophores could well be explained by exciton coupling theory. In the linear chromophore arrangements we also found superradiance of fluorescence but not in the branched systems. Furthermore, the 2PA showed enhanced cross sections for the linear oligomers but only additivity for the branched systems. This emphasizes that the enhancement of the 2PA cross section in the linear arrangements is probably caused by orbital interactions of higher excited configurations