Functional expression of human HMG-CoA reductase inSaccharomyces cerevisiae: a system to analyse normal and mutated versions of the enzyme in the context of statin treatment
| Autor: | Marek Kiliszek, Monika Maciag, Agata Leszczynska, Monika Wysocka-Kapcinska, Beata Burzynska, Danuta Plochocka, Joanna Rytka, J. Lutyk-Nadolska |
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| Rok vydání: | 2009 |
| Předmět: |
7-Dehydrocholesterol reductase
Mutant Saccharomyces cerevisiae Context (language use) Reductase Polymerase Chain Reaction Applied Microbiology and Biotechnology HMGB2 Protein Humans HMGB1 Protein Gene DNA Primers chemistry.chemical_classification Genetics biology Exons General Medicine biology.organism_classification Enzyme chemistry Biochemistry Cardiovascular Diseases HMG-CoA reductase Mutagenesis Site-Directed biology.protein Hydroxymethylglutaryl CoA Reductases Hydroxymethylglutaryl-CoA Reductase Inhibitors Biotechnology |
| Zdroj: | Journal of Applied Microbiology. 106:895-902 |
| ISSN: | 1365-2672 1364-5072 |
| DOI: | 10.1111/j.1365-2672.2008.04060.x |
| Popis: | Aims: Statins – inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase – are known to reduce blood cholesterol levels. In this paper, we present a Saccharomyces cerevisiae expression system, which enables quick evaluation of the sensitivity of the wild-type and/or mutant forms of human HMG-CoA reductase towards statins or other drugs. Methods and results: We analysed the sequence of the HMG-CoA reductase gene in DNA extracted from blood samples of 16 patients with cardiovascular disorders. We applied the yeast system to examine the sensitivity of the wild-type and mutated versions of the hHMG-CoA reductase to different types of statins. Conclusion: The yeast and mammalian HMG-CoA reductases demonstrate structural and functional conservation, and expression of human HMG-CoA reductase in yeast complements the lethal phenotype of strains lacking the HMG1 and HMG2 genes. Significance and Impact of the Study: These data indicate that a yeast expression system can serve to study the influence of selected mutations in human HMG-CoA reductase on the sensitivity of the enzyme to commonly prescribed statins. Our results suggest that this model system is suitable for the development and selection of lipid-lowering drugs as well as for the examination of DNA sequence variations in the context of statin therapy. |
| Databáze: | OpenAIRE |
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