PDBsum entry 3dy4

Hydrolase

PDB id: 3dy4

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

SLA ×4

Waters ×980

* Residue conservation analysis

PDB id:

3dy4

Name:

Hydrolase

Title:

Crystal structure of yeast 20s proteasome in complex with spirolactacystin

Structure:

Proteasome component y7. Chain: a, o. Synonym: macropain subunit y7, proteinase ysce subunit 7, multicatalytic endopeptidase complex subunit y7. Proteasome component y13. Chain: b, p. Fragment: unp residues 2-245. Synonym: macropain subunit y13, proteinase ysce subunit 13, multicatalytic endopeptidase complex subunit y13.

Source:

Saccharomyces cerevisiae. Baker's yeast. Organism_taxid: 4932. Cell_line: native purification. Other_details: 20s proteasome was prepared from yeast under native conditions. Conditions

Resolution:

2.80Å R-factor: 0.227 R-free: 0.256

Authors:

M.Groll,E.Balskus,E.Jacobsen

Key ref:

M.Groll et al. (2008). Structural analysis of spiro beta-lactone proteasome inhibitors. J Am Chem Soc, 130, 14981-14983. PubMed id: 18928262

Date:

25-Jul-08 Release date: 04-Nov-08

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, 1, 2: E.C.3.4.25.1 - proteasome endopeptidase complex.
• Reaction: Cleavage at peptide bonds with very broad specificity.

J Am Chem Soc 130:14981-14983 (2008)

PubMed id: 18928262

Structural analysis of spiro beta-lactone proteasome inhibitors.

M.Groll, E.P.Balskus, E.N.Jacobsen.

ABSTRACT

Spiro beta-lactone-based proteasome inhibitors were discovered in the context of an asymmetric catalytic total synthesis of the natural product (+)-lactacystin (1). Lactone 4 was found to be a potent inhibitor of the 26S proteasome, while its C-6 epimer (5) displayed weak activity. Crystallographic studies of the two analogues covalently bound to the 20S proteasome permitted characterization of the important stabilizing interactions between each inhibitor and the proteasome's key catalytic N-terminal threonine residue. This structural data support the hypothesis that the discrepancy in potency between 4 and 5 may be due to differences in the hydrolytic stabilities of the resulting acyl enzyme complexes.