Molecular Cloning and Expression of the cDNAs Encoding Human and Yeast Mevalonate Pyrophosphate Decarboxylase
Matthew J. Toth‡ and Leslie Huwyler
01/05/2011
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.