Mycocypins, clitocypins and macrocypins, are cysteine protease inhibitors isolated from the mushrooms Clitocybe nebularis and Macrolepiota procera. Lack of sequence homology to other families of ...protease inhibitors suggested that mycocypins inhibit their target cysteine protease by a unique mechanism and that a novel fold may be found. The crystal structures of the complex of clitocypin with the papain-like cysteine protease cathepsin V and of macrocypin and clitocypin alone have revealed yet another motif of binding to papain like-cysteine proteases, which in a yet unrevealed way occludes the catalytic residue. The binding is associated with a peptide-bond flip of glycine that occurs before or concurrently with the inhibitor docking. Mycocypins possess a β-trefoil fold, the hallmark of Kunitz-type inhibitors. It is a tree-like structure with two loops in the root region, a stem comprising a six-stranded β-barrel, and two layers of loops (6 + 3) in the crown region. The two loops that bind to cysteine cathepsins belong to the lower layer of the crown loops, whereas a single loop from the crown region can inhibit trypsin or asparaginyl endopeptidase, as demonstrated by site-directed mutagenesis. These loops present a versatile surface with the potential to bind to additional classes of proteases. When appropriately engineered, they could provide the basis for possible exploitation in crop protection.
Economic growth and development depend more and more on technological advancements achieved primarily through intangible capital and knowledge. Brain drain, as the literature usually labels the ...emigration of highly skilled resources, is primarily triggered by better job and material opportunities abroad, in the comparatively more developed economies. The paper explores the issue of brain drain among a highly specific group of young skilled professionals in Slovenia: those young researchers who have been included in the national Young Researchers Funding Scheme. Using qualitative methodology on a sample of the past and current participants in the national Young Researchers Funding Scheme, the authors search for the answer by examining the education and career paths of the young Slovenian researchers, their domestic and foreign educational and work experience, as well as the pull and push factors influencing their decision to study and/or work abroad.
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