3DY4: Crystal Structure Of Yeast 20s Proteasome In Complex With Spirolactacystin

Citation:
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.
PDB ID: 3DY4Download
MMDB ID: 67758
PDB Deposition Date: 2008/7/25
Updated in MMDB: 2008/11
Experimental Method:
x-ray diffraction
Resolution: 2.8  Å
Source Organism:
Similar Structures:
Biological Unit for 3DY4: 28-meric; determined by author and by software (PISA)
Molecular Components in 3DY4
Label Count Molecule
Proteins (28 molecules)
2
Proteasome Component Y7(Gene symbol: PRE8)
Molecule annotation
2
Proteasome Component Y13(Gene symbol: PRE9)
Molecule annotation
2
Proteasome Component Pre6(Gene symbol: PRE6)
Molecule annotation
2
Proteasome Component Pup2(Gene symbol: PUP2)
Molecule annotation
2
Proteasome Component Pre5(Gene symbol: PRE5)
Molecule annotation
2
Proteasome Component C1(Gene symbol: PRE10)
Molecule annotation
2
Proteasome Component C7-alpha(Gene symbol: SCL1)
Molecule annotation
2
Proteasome Component Pup1(Gene symbol: PUP1)
Molecule annotation
2
Proteasome Component Pup3(Gene symbol: PUP3)
Molecule annotation
2
Proteasome Component C11(Gene symbol: PRE1)
Molecule annotation
2
Proteasome Component Pre2(Gene symbol: PRE2)
Molecule annotation
2
Proteasome Component C5(Gene symbol: PRE7)
Molecule annotation
2
Proteasome Component Pre4(Gene symbol: PRE4)
Molecule annotation
2
Proteasome Component Pre3(Gene symbol: PRE3)
Molecule annotation
Chemicals (4 molecules)
1
4
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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