About: Mechanism of modulation of cytochrome P450 1A1/2 mediated oxidation of drugs and carcinogens by cytochrome b5; experimental and computational approach     Goto   Sponge   NotDistinct   Permalink

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Description
  • Cytochromes P450 (CYPs) represent a large and important group of enzymes oxidizing majority of drugs and carcinogens. Eukaryotic CYPs act in tight cooperation with other proteins in the membrane of endoplasmic reticulum. One of them, cytochrome b5 (cyt b5), was reported to enhance, inhibit, or has no effect on catalysis by CYPs, depending on the specific CYP and the substrate. The project addresses still unsettled questions regarding the mechanism of a cyt b5-mediated stimulatory effect on CYP1A-catalyzed oxidation of several substrates (Sudan I, benzo[a]pyrene, ellipticine, ethoxyresorufin, methoxyresorufin). Effect of various forms of cyt b5 (native microsomal-, soluble recombinant-, apo- and Mn-protoporphyrin IX cyt b5 variants) on CYP1A-mediated catalysis, structure and substrate affinity will be studied using combination of computational and experimental biochemical techniques. The resolution of the project will have practical importance as it would help to improve approach the in vitro study to in vivo situation as well as to contribute to elucidation of CYP reaction mechanism. (en)
  • Vysvětlení mechanismu modulace oxidace biologicky významných substrátů cytochromů P450 1A1/2 působením různých forem cytochromu b5 (nativní mikrosomální cyt b5, solubilní rekombinantní cyt b5, apo-forma cyt b5 a cyt b5 obsahující Mn-protoporphyrin IX) pomocí teoretických i experimentálních technik.
Title
  • Mechanism of modulation of cytochrome P450 1A1/2 mediated oxidation of drugs and carcinogens by cytochrome b5; experimental and computational approach (en)
  • Mechanismus modulace oxidace léčiv a karcinogenů cytochromy P450 1A1/2 působením cytochromu b5; experimentální i teoretické přístupy
skos:notation
  • GA203/09/0812
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  • cytochrom P450, NADPH:CYP reduktasa, cytochrom b5, substráty (en)
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  • Řešení projektu proběhlo výtečně, jak z hlediska odborného tak i z hlediska čerpání finančních prostředků. (cs)
  • The project was excellent, both in terms of expertise and in terms of disbursement of funds. (en)
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  • NADPH:CYP reduktasa
  • cytochrom b5
  • cytochrom P450
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