. . . . "0"^^ . . "Presented grant proposal is focused on structure-function relationship study of cytochromes P450 (P450), key enzymes involved in metabolism of foreign compounds, e.g. drugs, and carcinogen activation. The aim of the project is a validation of an experimental and theoretical P450 model systems frequently used for drug development and carcinogen risk assessment. To accomplish this task a combination of research techniques investigating the native structure of enzyme as well as their metabolic activities will be used. Research strategy of the enzyme structure is based on application of chemical cross-linking reagents followed by mass spectroscopy. This approach is able to provide structural information of native enzyme in membrane environment in contact with reaction partners. This is the major advantage of cross-linking in contrary to e.g. X-ray crystallography or NMR methods working either with crystal or the enzyme in artificial conditions. Using revealed structural parameters of native"@en . . . " native structure" . "cytochrome P450; native structure; cross-linking reagents; mass spectroscopy; drug metabolism"@en . . "20"^^ . "cytochrome P450" . "20"^^ . "GA303/06/0928" . . "2009-10-22+02:00"^^ . "\u0158e\u0161itelsk\u00FD kolektiv v pr\u016Fb\u011Bhu \u0159e\u0161en\u00ED projektu sledoval schv\u00E1len\u00FD v\u00FDzkumn\u00FD z\u00E1m\u011Br studia vztahu struktury a funkce cytochrom\u016F P450. C\u00EDle projektu byly v pl\u00E1novan\u00FDch sm\u011Brech spln\u011Bny a v \u0159ad\u011B ohled\u016F i p\u0159ekro\u010Deny. \u0158e\u0161en\u00ED projektu p\u0159ineslo celou \u0159adu origin\u00E1ln"@cs . "2008-12-31+01:00"^^ . . . . "http://www.isvav.cz/projectDetail.do?rowId=GA303/06/0928"^^ . . . "2008-04-25+02:00"^^ . . "Research team followed the approved plan of the research focused on structure-function relationships of cytochromes P450 in the proposed time shedule. The project aims were accomplished in full and in some regards even exceeded. Original results obtained"@en . . "Studium vztahu struktury a funkce cytochrom\u016F P450 - st\u011B\u017Eejn\u00EDch enzym\u016F metabolismu l\u00E9\u010Div a aktivace karcinogen\u016F" . . " cross-linking reagents" . . "Study on structure-function relationship of cytochromes P450 - key enzymes involved in drug metabolism and carcinogen activation"@en . " mass spectroscopy" . "P\u0159edkl\u00E1dan\u00FD projekt je zam\u011B\u0159en na \u0159e\u0161en\u00ED vztahu struktury a funkce cytochrom\u016F P450 (P450), enzym\u016F, kter\u00E9 maj\u00ED kl\u00ED\u010Dov\u00FD v\u00FDznam p\u0159i metabolismu cizorod\u00FDch l\u00E1tek, nap\u0159. l\u00E9\u010Div, a aktivaci karcinogen\u016F. C\u00EDlem projektu je validace experiment\u00E1ln\u00EDch a teoretick\u00FDchmodelov\u00FDch syst\u00E9m\u016F cytochromu P450, kter\u00E9 jsou pou\u017E\u00EDv\u00E1ny zejm\u00E9na v procesu v\u00FDvoje l\u00E9\u010Div \u010Di testov\u00E1n\u00ED karcinogen\u016F. K realizaci tohoto z\u00E1m\u011Bru poslou\u017E\u00ED kombinace postup\u016F studia nativn\u00ED prostorov\u00E9 struktury a metabolick\u00FDch parametr\u016F P450. Zvolen\u00E1 strategie studia struktury P450 technikou chemick\u00E9ho zes\u00EDt\u011Bn\u00ED s n\u00E1slednou anal\u00FDzou kovalentn\u011B propojen\u00FDch m\u00EDst pomoc\u00ED hmotnostn\u00ED spektrometrie umo\u017En\u00ED (na rozd\u00EDl od nap\u0159. %22X-ray%22 krystalografie a NMR technik) studovat nativn\u00ED P450 v interakc\u00EDch s vazebn\u00FDmi partnerycel\u00E9ho enzymov\u00E9ho syst\u00E9mu v jejich p\u0159irozen\u00E9m prost\u0159ed\u00ED membr\u00E1ny a tak odhalit organizaci membr\u00E1nov\u00E9 mikrodom\u00E9ny P450 a vytvo\u0159it jej\u00ED prostorov\u00FD model. Tyto znalosti strukturn\u00EDch parametr\u016F, kter\u00E9 jsou z\u00E1sadn\u00ED pro metabolickou aktivitu P450, umo\u017En\u00ED" . "1"^^ . "1"^^ . "2006-01-01+01:00"^^ .