PDBsum entry 4q1s

Hydrolase/toxin

PDB id: 4q1s

Contents

Protein chains

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.

Ligands

2YD ×2

Waters ×1310

PDB id:

4q1s

Name:

Hydrolase/toxin

Title:

Yeast 20s proteasome in complex with kendomycin

Structure:

Proteasome subunit alpha type-2. Chain: a, o. Synonym: macropain subunit y7, multicatalytic endopeptidase complex subunit y7, proteasome component y7, proteinase ysce subunit 7. Proteasome subunit alpha type-3. Chain: b, p. Synonym: macropain subunit y13, multicatalytic endopeptidase complex subunit y13, proteasome component y13, proteinase ysce subunit 13. Proteasome subunit alpha type-4.

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 559292. Strain: atcc 204508 / s288c. Strain: atcc 204508 / s288c

Resolution:

2.60Å R-factor: 0.178 R-free: 0.224

Authors:

P.Beck,W.Heinemeyer,A.Spaeth,Y.Elnakady,R.Mueller,M.Groll

Key ref:

P.Beck et al. (2014). Interactions of the natural product kendomycin and the 20S proteasome. J Mol Biol, 426, 3108-3117. PubMed id: 25038530 DOI: 10.1016/j.jmb.2014.06.019

Date:

04-Apr-14 Release date: 30-Jul-14

Protein chains

P23639  (PSA2_YEAST) -  Proteasome subunit alpha type-2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 250 a.a.

Struc: 250 a.a.

Protein chains

P23638  (PSA3_YEAST) -  Proteasome subunit alpha type-3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 258 a.a.

Struc: 244 a.a.

Protein chains

P40303  (PSA4_YEAST) -  Proteasome subunit alpha type-4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 254 a.a.

Struc: 241 a.a.

Protein chains

P32379  (PSA5_YEAST) -  Proteasome subunit alpha type-5 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 260 a.a.

Struc: 242 a.a.

Protein chains

P40302  (PSA6_YEAST) -  Proteasome subunit alpha type-6 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 234 a.a.

Struc: 233 a.a.

Protein chains

P21242  (PSA7_YEAST) -  Probable proteasome subunit alpha type-7 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 288 a.a.

Struc: 244 a.a.

Protein chains

P21243  (PSA1_YEAST) -  Proteasome subunit alpha type-1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 252 a.a.

Struc: 243 a.a.

Protein chains

P25043  (PSB2_YEAST) -  Proteasome subunit beta type-2 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 261 a.a.

Struc: 222 a.a.

Protein chains

P25451  (PSB3_YEAST) -  Proteasome subunit beta type-3 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 205 a.a.

Struc: 204 a.a.

Protein chains

P22141  (PSB4_YEAST) -  Proteasome subunit beta type-4 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 198 a.a.

Struc: 198 a.a.

Protein chains

P30656  (PSB5_YEAST) -  Proteasome subunit beta type-5 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 287 a.a.

Struc: 212 a.a.

Protein chains

P23724  (PSB6_YEAST) -  Proteasome subunit beta type-6 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 241 a.a.

Struc: 222 a.a.

Protein chains

P30657  (PSB7_YEAST) -  Proteasome subunit beta type-7 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 266 a.a.

Struc: 233 a.a.

Protein chains

P38624  (PSB1_YEAST) -  Proteasome subunit beta type-1 from Saccharomyces cerevisiae (strain ATCC 204508 / S288c)

Seq: 215 a.a.

Struc: 196 a.a.

Enzyme reactions

• Enzyme class: Chains A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P, Q, R, S, T, U, V, W, X, Y, Z, a, b: E.C.3.4.25.1 - proteasome endopeptidase complex.
• Reaction: Cleavage at peptide bonds with very broad specificity.

DOI no: 10.1016/j.jmb.2014.06.019

J Mol Biol 426:3108-3117 (2014)

PubMed id: 25038530

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

P.Beck, W.Heinemeyer, A.L.Späth, Y.Elnakady, R.Müller, M.Groll.

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.