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

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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.