Brennan S O, Peach R J
Pathology Department, Christchurch School of Medicine, Christchurch Hospital, New Zealand.
FEBS Lett. 1988 Feb 29;229(1):167-70. doi: 10.1016/0014-5793(88)80819-6.
The yeast KEX2 protease is the only enzyme that has a proven role in the activation of polypeptide hormones through cleavage at pairs of basic residues. The enzyme that fulfils this role in higher eukaryotes has yet to be unequivocally identified. In this investigation, a KEX2-like calcium-dependent protease has been identified in rat hepatic microsomes. The enzyme is membrane-bound, has a pH optimum of 5-6 and converts proalbumin to albumin. More importantly, like the KEX2 protease, it meets two other exacting criteria defined by specific mutations in humans. Namely, it does not process proalbumin Christchurch (-1 Arg----Gln) which lacks one of the requisite basic residues and, whilst not itself a serine protease, it is inhibited by the reactive center variant, alpha 1-antitrypsin Pittsburgh (358 Met----Arg) but not by normal alpha 1-antitrypsin.
酵母KEX2蛋白酶是唯一一种经证实可通过在碱性氨基酸残基对处切割来激活多肽激素的酶。在高等真核生物中发挥这一作用的酶尚未得到明确鉴定。在本研究中，在大鼠肝微粒体中鉴定出一种类似KEX2的钙依赖性蛋白酶。该酶与膜结合，最适pH为5 - 6，可将前清蛋白转化为清蛋白。更重要的是，与KEX2蛋白酶一样，它符合人类特定突变所定义的另外两个严格标准。也就是说，它不处理缺少必需碱性残基之一的克赖斯特彻奇前清蛋白（-1 Arg----Gln），并且，虽然它本身不是丝氨酸蛋白酶，但它被反应中心变体α1 - 抗胰蛋白酶匹兹堡（358 Met----Arg）抑制，而不被正常的α1 - 抗胰蛋白酶抑制。
