PRESEQUENCE PEPTIDASE IN NATIVE OR COMPLEXED WITH SUBSTRATES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 前序肽酶(PREP)是一种117kDa的锌金属蛋白水解酶，能降解与阿尔茨海默病、S病有关的淀粉样β蛋白。此外，Prep被认为在输入到基质中后调节线粒体的靶向序列。来自植物同源基因、AtPreP和同源模型的结构研究表明，人类PREP具有一个可能在底物选择性中发挥作用的内室(隐窝)。再加上生化研究，这种酶用于治疗阿尔茨海默病-S病的适合性将通过结构研究得到极大的提高，从而增强对Prep如何选择和降解其底物的机制的理解。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Presequence peptidase (PreP) is a 117-kDa zinc metalloprotease that degrades amyloid-beta (Aβ), a peptide implicated in Alzheimer?s disease. Additionally, PreP has been postulated to regulate mitochondrial targeting sequences after import into the matrix. Structural studies from the plant homolog, AtPreP, and homology modeling suggest that human PreP possesses an inner chamber (crypt) that may play a role in substrate selectivity. Coupled with biochemical studies, the suitability of this protease for therapeutic development towards Alzheimer?s disease will be greatly enhanced by structural studies that give an enhanced understanding of the mechanisms of how PreP selects and degrades its substrates.