UBIQUITIN C-TERMINAL HYDROLASE L3 COMPLEX WITH UBIQUITIN-BASED SUICIDE SUBSTRATE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 一种控制引起疟疾的恶性疟原虫的新方法针对寄生虫的泛素-蛋白酶体途径，这是其生存所必需的。由于宿主对病原体的防御机制依赖于泛素-蛋白酶体系统在抗原呈递和膜运输的调节中，许多病毒和细菌编码作用于泛素-蛋白酶体途径的蛋白质，但在寄生虫中几乎完全缺乏关于该途径的数据。 结果表明，恶性疟原虫中的哺乳动物UchL 3直系同源物（PfUchL 3）具有去泛素化以及去泛素化活性。我们有兴趣确定PfUchL 3的分子结构，并揭示对泛素和NEDD 8的双重特异性的机制。为此，我们制备了PfUchL 3和基于泛素的硅化物底物UbVME之间的复合物的晶体。

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. A new approach to controlling malaria-causing Plasmodium falciparum aims at the parasite's ubiquitin-proteasome pathway which is essential for its survival. Since the host's defense mechanisms against pathogens rely on the ubiquitin-proteasome system in antigen presentation and in the regulation of membrane trafficking, many viruses and bacteria encode proteins that act on the ubiquitin-proteasome pathway, yet there is a near-complete lack of data on this pathway in parasites. It was shown that the mammalian UchL3 ortholog in Plasmodium falciparum (PfUchL3) possesses deubiquitinating as well as deNeddylating activity. We are interested in determining the molecular architecture of PfUchL3 and revealing the mechanisms for the dual specificity towards ubiquitin and NEDD8. To this end we prepared crystals of the complex between PfUchL3 and the ubiquitin based suicide substrate UbVME.