Mizuno K, Matsuo H
Nature. 1984;309(5968):558-60. doi: 10.1038/309558a0.
Paired basic residues have been observed as sites of proteolytic processing of prohormones in a wide range of eukaryotic species. This strongly suggests that proteases exhibiting specificity towards paired basic residues may be involved in prohormone processing, but candidate enzymes have not so far been identified. Yeast Saccharomyces cerevisiae alpha-cells synthesize and secrete alpha-mating factor, a peptide of 13 amino acids, the processing of which from a larger precursor involves cleavage at paired basic residues (-Lys-Arg-). We have therefore used them as a simple model system for the study of prohormone processing and report here the identification, in cell lysates, of a novel protease which specifically recognizes and cleaves the peptide bonds between consecutive basic residues. The purified enzyme, which we have called propheromone -convertase Y, has a molecular weight (MW) of around 43,000. It cleaves various peptide substrates at paired basic residues, but not at single basic residues, implying it is distinct from trypsin-like proteases. Its unique substrate specificity suggests the enzyme may be involved in propheromone processing in vivo.
在多种真核生物中，已观察到成对的碱性残基是激素原蛋白水解加工的位点。这有力地表明，对成对碱性残基具有特异性的蛋白酶可能参与激素原的加工，但迄今为止尚未鉴定出候选酶。酿酒酵母α细胞合成并分泌α-交配因子，这是一种由13个氨基酸组成的肽，其从较大前体的加工过程涉及在成对碱性残基（-Lys-Arg-）处的切割。因此，我们将它们用作研究激素原加工的简单模型系统，并在此报告在细胞裂解物中鉴定出一种新型蛋白酶，该蛋白酶能特异性识别并切割连续碱性残基之间的肽键。我们将纯化的酶称为前激素原转化酶Y，其分子量（MW）约为43,000。它在成对碱性残基处切割各种肽底物，但不在单个碱性残基处切割，这意味着它与胰蛋白酶样蛋白酶不同。其独特的底物特异性表明该酶可能在体内参与前激素原的加工。
