4Q1S

Yeast 20S proteasome in Complex with Kendomycin

Summary for 4Q1S

• Entry DOI: 10.2210/pdb4q1s/pdb
• Related: 1RYP
• Descriptor: Proteasome subunit alpha type-2, Proteasome subunit beta type-4, Proteasome subunit beta type-5, ... (16 entities in total)
• Functional Keywords: proteasome, natural product, quinone methide, covalent binding, exosite, hydrolase-toxin complex, hydrolase/toxin
• Biological source: Saccharomyces cerevisiae (Baker's yeast); More
• Cellular location: Cytoplasm: P23639 P22141 P30656 P23724 P30657 P38624 P23638 P40303 P32379 P40302 P21242 P21243 P25043 P25451
• Total number of polymer chains: 28
• Total formula weight: 732028.08

Authors

Beck, P.,Heinemeyer, W.,Spaeth, A.,Elnakady, Y.,Mueller, R.,Groll, M. (deposition date: 2014-04-04, release date: 2014-07-30, Last modification date: 2024-11-06)

Primary citation

Beck, P.,Heinemeyer, W.,Spath, A.L.,Elnakady, Y.,Muller, R.,Groll, M.
Interactions of the natural product kendomycin and the 20S proteasome.
J.Mol.Biol., 426:3108-3117, 2014

PubMed 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.

PubMed: 25038530
DOI: 10.1016/j.jmb.2014.06.019

Experimental method

X-RAY DIFFRACTION (2.6 Å)