"Modulation of enzymatic activity in cathepsins"@en . . . . . "2007-09-26+02:00"^^ . "cathepsin; inhibitor; activity regulation"@en . "0"^^ . . "0"^^ . . "Identifikovali jsme nov\u00E9 modul\u00E1tory aktivity kathepsinov\u00FDch proteas s inhibi\u010Dn\u00ED nebo aktiva\u010Dn\u00ED funkc\u00ED. Tyto molekuly p\u0159edstavuj\u00ED perspektivn\u00ED n\u00E1stroje pro regulaci patologick\u00FDch proces\u016F, kter\u00FDch se kathepsiny \u00FA\u010Dastn\u00ED."@cs . "Failure to control lysosomal proteases (cathepsins) activity leads to pathological conditions. This project focuses on cathepsin C (modulator of immunocompetent cells) and cathepsin D (involved in breast cancer and neuropathology) and investigates structure-function relationship with regards to in vivo regulation of their enzymatic activity. Maturation processing, interaction with activators and inhibitors will be studied by enzymology, protein-chemistry methods and 3D modeling. The structural scaffolds of discovered regulatory determinants will be used for design of novel low molecular weight inhibitors specific to these enzymes. We also study cathepsin-like enzymes critical for human parasites, allergen producers and insect pests. Their inhibition will be analyzed on moleculat level as a tool for development of suppression strategies. The project will provide new information how activity of cathepsins is regulated in vivo and can be modulated in potential therapeutic applications."@en . "1"^^ . . . . . . . . "http://www.isvav.cz/projectDetail.do?rowId=IAA4055303"^^ . . "Porucha regulace lysosom\u00E1ln\u00EDch proteas (kathepsin\u016F) je p\u0159\u00ED\u010Dinou v\u00E1\u017En\u00FDch patologick\u00FDch stav\u016F. C\u00EDlem projektu je analysa molekuly kathepsinu C (modul\u00E1toru imunitn\u00EDch bun\u011Bk) a kathepsinu D (spojen\u00E9ho s rakovinou prsu a neuropatologi\u00ED) pokud jde o vztah struktury a funkce p\u0159i regulaci jejich aktivity in vivo. Pomoc\u00ED enzymologick\u00FDch, proteinov\u011B chemick\u00FDch metod a modelov\u00E1n\u00ED 3D struktur bude studov\u00E1n aktiva\u010Dn\u00ED processing a interakce s inhibitory a aktiv\u00E1tory. Nalezen\u00E9 regula\u010Dn\u00ED struktury budou pou\u017Eity pro design a synt\u00E9zu nov\u00FDch n\u00EDzkomolekul\u00E1rn\u00EDch inhibitor\u016F specifick\u00FDch pro tyto enzymy. D\u00E1le budou analysov\u00E1ny v\u00FDznamn\u00E9 enzymy p\u0159\u00EDbuzn\u00E9 kathepsin\u016Fm u vybran\u00FDch bezobratl\u00FDch (parazit\u016F \u010Dlov\u011Bka, zdroj\u016F alergen\u016F a hmyz\u00EDch \u0161k\u016Fdc\u016F) a jejich inhibice na molekul\u00E1rn\u00ED \u00FArovni jako prost\u0159edek vyu\u017Eiteln\u00FD v ochrann\u00FDch strategi\u00EDch. Projekt poskytne informace o regulaci aktivity kathepsin\u016F, jej\u00ED roli v patogenesi a nov\u00FDch slou\u010Denin\u00E1ch s potenci\u00E1ln\u00ED terapeutickou aplikac\u00ED." . . "We identified new modulators of activity of cathepsin proteases with inhibitory or activatory function. These molecules represent promising tools for regulation of cathepsin-dependent pathologic processes."@en . . " inhibitor" . "5"^^ . . "5"^^ . "Modulace enzymov\u00E9 aktivity kathepsin\u016F" . "IAA4055303" . . "cathepsin" . .