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Interactions of the natural product kendomycin and the 20S proteasome.

Abstract：

:Natural 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 (KM) 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 KM-proteasome interactions in vitro and in vivo, including complex structures of wild type and mutant yeast 20S proteasome with KM. Our results provide evidence for a polypharmacological mode of action for KM's cytotoxic effect on cancer cells.

journal_name

J Mol Biol

journal_title

Journal of molecular biology

authors

Beck P,Heinemeyer W,Späth AL,Elnakady Y,Müller R,Groll M

doi

10.1016/j.jmb.2014.06.019

subject

Has Abstract

pub_date

2014-09-09 00:00:00

pages

3108-3117

issue

18

eissn

0022-2836

issn

1089-8638

pii

S0022-2836(14)00335-0

journal_volume

426

pub_type

杂志文章

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