 |
PDBsum entry 4q1s
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Hydrolase/toxin
|
PDB id
|
|
|
|
4q1s
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
Contents |
 |
|
|
|
|
|
|
|
|
|
|
|
250 a.a.
|
|
|
|
|
|
|
|
|
|
|
244 a.a.
|
|
|
|
|
|
|
|
|
|
|
241 a.a.
|
|
|
|
|
|
|
|
|
|
|
242 a.a.
|
|
|
|
|
|
|
|
|
|
|
233 a.a.
|
|
|
|
|
|
|
|
|
|
|
244 a.a.
|
|
|
|
|
|
|
|
|
|
|
243 a.a.
|
|
|
|
|
|
|
|
|
|
|
222 a.a.
|
|
|
|
|
|
|
|
|
|
|
204 a.a.
|
|
|
|
|
|
|
|
|
|
|
198 a.a.
|
|
|
|
|
|
|
|
|
|
|
212 a.a.
|
|
|
|
|
|
|
|
|
|
|
222 a.a.
|
|
|
|
|
|
|
|
|
|
|
233 a.a.
|
|
|
|
|
|
|
|
|
|
|
196 a.a.
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Interactions of the natural product kendomycin and the 20s proteasome.
|
|
|
Authors
|
|
P.Beck,
W.Heinemeyer,
A.L.Späth,
Y.Elnakady,
R.Müller,
M.Groll.
|
|
|
Ref.
|
|
J Mol Biol, 2014,
426,
3108-3117.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
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.
|
|
|
|
|
|
|
