Toth M J, Huwyler L
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901, USA.
J Biol Chem. 1996 Apr 5;271(14):7895-8. doi: 10.1074/jbc.271.14.7895.
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.
降低血清胆固醇水平对预防心血管疾病的重要性已有充分记录。由于甲羟戊酸焦磷酸脱羧酶是胆固醇生物合成途径中的一种独特酶，它是治疗高胆固醇血症和其他疾病的潜在治疗靶点。因此，我们克隆并表达了人类该酶的cDNA。我们还利用人类酶与先前未鉴定的不完整基因组序列的相似性克隆并表达了酵母同源物。Northern印迹分析显示在多种人类组织中存在约2千碱基的转录本。重组人类酶是由43-kDa亚基组成的同型二聚体，比活性为2.4单位/毫克。与已知序列进行的计算机相似性搜索表明，甲羟戊酸焦磷酸脱羧酶与其他蛋白质的相似性很小。
