Structural highlights
FunctionPSA2_YEAST The proteasome degrades poly-ubiquitinated proteins in the cytoplasm and in the nucleus. It is essential for the regulated turnover of proteins and for the removal of misfolded proteins. The proteasome is a multicatalytic proteinase complex that is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. It has an ATP-dependent proteolytic activity. Publication Abstract from PubMedNatural products are a valuable source for novel lead structures in drug discovery, but for the majority of isolated bioactive compounds the cellular targets are unknown. The structurally unique ansa-polyketide kendomycin was reported to exert its potent cytotoxic effects via impairment of the ubiquitin proteasome system, but the exact mode of action remained unclear. Here, we present a systematic biochemical characterization of kendomycin-proteasome interactions in vitro as well as in vivo, including complex structures of wildtype and mutant yeast 20S proteasome with kendomycin. Our results provide evidence for a polypharmacological mode of action for kendomycin's cytotoxic effect on cancer cells. Structural and biochemical characterization of the natural product kendomycin and the 20S proteasome.,Beck P, Heinemeyer W, Spath AL, Elnakady Y, Muller R, Groll M J Mol Biol. 2014 Jul 16. pii: S0022-2836(14)00335-0. doi:, 10.1016/j.jmb.2014.06.019. PMID:25038530[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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