Premium
Functional expression of human HMG‐CoA reductase in Saccharomyces cerevisiae : a system to analyse normal and mutated versions of the enzyme in the context of statin treatment
Author(s) -
WysockaKapcinska M.,
LutykNadolska J.,
Kiliszek M.,
Plochocka D.,
Maciag M.,
Leszczynska A.,
Rytka J.,
Burzynska B.
Publication year - 2009
Publication title -
journal of applied microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.889
H-Index - 156
eISSN - 1365-2672
pISSN - 1364-5072
DOI - 10.1111/j.1365-2672.2008.04060.x
Subject(s) - reductase , hmg coa reductase , saccharomyces cerevisiae , 7 dehydrocholesterol reductase , context (archaeology) , statin , biology , yeast , biochemistry , coenzyme a , enzyme , hydroxymethylglutaryl coa reductase , mutant , gene , paleontology
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.