PROTEASE PRO-REGION REQUIRED FOR FOLDING IS A POTENT INHIBITOR OF THE MATURE ENZYME
PROTEASE PRO-REGION REQUIRED FOR FOLDING IS A POTENT INHIBITOR OF THE MATURE ENZYME
复制标题
DOI：
10.1002/prot.340120406
复制
发表时间：
1992-04-01
期刊：
影响因子：
--
通讯作者：
AGARD, DA
中科院分区：
文献类型：
--
作者：
BAKER, D;SILEN, JL;AGARD, DA
α-裂解蛋白酶是一种细胞外细菌丝氨酸蛋白酶，其合成具有大的前区，该前区是蛋白酶结构域在体内正确折叠所需的。为了进行详细的机制研究，我们在体外重建了前区域依赖性折叠。在没有其他蛋白因子或外源能量来源的情况下，前区促进蛋白酶结构域的折叠。令人惊讶的是，我们发现前区是成熟蛋白酶的高亲和力抑制剂。pro区还抑制密切相关的灰色链霉菌蛋白酶B，但不抑制更远相关但结构相似的蛋白酶弹性蛋白酶。基于这些数据，我们提出了一种机制，其中亲区域结合降低了具有天然样结构的后期折叠过渡态的自由能。
Alpha-lytic protease, an extracellular bacterial serine protease, is synthesized with a large pro region that is required in vivo for the proper folding of the protease domain. To allow detailed mechanistic study, we have reconstituted pro region-dependent folding in vitro. The pro region promotes folding of the protease domain in the absence of other protein factors or exogenous energy sources. Surprisingly, we find that the pro region is a high affinity inhibitor of the mature protease. The pro region also inhibits the closely related Streptomyces griseus protease B, but not the more distantly related, yet structurally similar protease, elastase. Based on these data, we suggest a mechanism in which pro region binding reduces the free energy of a late folding transition state having native-like structure.