期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1990
卷号：87
期号：8
页码：2872-2876
DOI：10.1073/pnas.87.8.2872
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Mevalonate kinase [ATP:(R)-mevalonate 5-phosphotransferase, EC 2.7.1.36 ] may be a regulatory site in the cholesterol biosynthetic pathway, and a mutation in the gene coding for this enzyme is thought to cause the genetic disease mevalonic aciduria. To characterize this enzyme, a rat liver cDNA library was screened with a monospecific antibody, and a 1.7-kilobase cDNA clone coding for mevalonate kinase was isolated. The complete DNA sequence was determined, and the longest open reading frame coded for a protein containing 395 amino acids with a deduced molecular weight of 41,990. Identification of the cDNA clone was confirmed by expression of enzyme activity in yeast and by protein sequence data obtained from sequencing purified rat mevalonate kinase. The deduced amino acid sequence of mevalonate kinase contained a motif for the ATP-binding site found in protein kinases, and it also showed sequence homology to the yeast RAR1 protein. The size of mevalonate kinase mRNA in rat liver was approximately 2 kilobases. Treatment with diets containing cholesterol-lowering agents caused an increase in both mevalonate kinase activity and mRNA levels, whereas diets containing 5% cholesterol lowered the levels of both enzyme activity and mRNA. These data indicate that long-term regulation of enzyme activity in rat liver is controlled by changes in the levels of mevalonate kinase mRNA.
