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酶原转化为活性蛋白水解酶的分子机制。

Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes.

作者信息

Khan A R, James M N

机构信息

Department of Biochemistry, University of Alberta, Edmonton, Canada.

出版信息

Protein Sci. 1998 Apr;7(4):815-36. doi: 10.1002/pro.5560070401.

Abstract

Proteolytic enzymes are synthesized as inactive precursors, or "zymogens," to prevent unwanted protein degradation, and to enable spatial and temporal regulation of proteolytic activity. Upon sorting or appropriate compartmentalization, zymogen conversion to the active enzyme typically involves limited proteolysis and removal of an "activation segment." The sizes of activation segments range from dipeptide units to independently folding domains comprising more than 100 residues. A common form of the activation segment is an N-terminal extension of the mature enzyme, or "prosegment," that sterically blocks the active site, and thereby prevents binding of substrates. In addition to their inhibitory role, prosegments are frequently important for the folding, stability, and/or intracellular sorting of the zymogen. The mechanisms of conversion to active enzymes are diverse in nature, ranging from enzymatic or nonenzymatic cofactors that trigger activation, to a simple change in pH that results in conversion by an autocatalytic mechanism. Recent X-ray crystallographic studies of zymogens and comparisons with their active counterparts have identified the structural changes that accompany conversion. This review will focus upon the structural basis for inhibition by activation segments, as well as the molecular events that lead to the conversion of zymogens to active enzymes.

摘要

蛋白水解酶以无活性的前体形式,即“酶原”进行合成,以防止不必要的蛋白质降解,并实现蛋白水解活性的空间和时间调控。在分选或进行适当的区室化后,酶原转化为活性酶通常涉及有限的蛋白水解作用以及去除一个“激活片段”。激活片段的大小范围从二肽单元到包含100多个残基的独立折叠结构域。激活片段的一种常见形式是成熟酶的N端延伸,即“前肽”,它在空间上阻断活性位点,从而防止底物结合。除了其抑制作用外,前肽对于酶原的折叠、稳定性和/或细胞内分选通常也很重要。转化为活性酶的机制本质上多种多样,从触发激活的酶促或非酶促辅因子,到导致通过自催化机制进行转化的简单pH变化。最近对酶原的X射线晶体学研究以及与其活性对应物的比较已经确定了伴随转化的结构变化。本综述将重点关注激活片段抑制作用的结构基础,以及导致酶原转化为活性酶的分子事件。

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