Molecular Cloning and Expression of the cDNAs Encoding Human and Yeast Mevalonate Pyrophosphate Decarboxylase

The importance of lowering serum cholesterol levels for the prevention of cardiovascular disease has been well documented. Because mevalonate pyrophosphate decarboxylase is a unique enzyme in the cholesterol biosynthetic pathway it is a potential therapeutic target for the treatment of hypercholesterolemia and other diseases. For this reason we cloned and expressed the cDNA for the human enzyme. We also cloned and expressed the yeast homolog using the human enzyme’s similarity to a previously unidentified and incomplete genomic sequence. Northern blot analysis revealed a transcript of approximately 2 kilobases in a variety of human tissues. The recombinant human enzyme is a homodimer of 43-kDa subunits with a specific activity of 2.4 units/mg. Computer searches for similarity with known sequences showed that mevalonate pyrophosphate decarboxylase has little similarity to other proteins.