4MDK: Cdc34-ubiquitin-cc0651 Complex

Citation:
Abstract
Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small-molecule inhibitor of the E2 ubiquitin-conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin-binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester without decreasing the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities.
PDB ID: 4MDKDownload
MMDB ID: 115889
PDB Deposition Date: 2013/8/22
Updated in MMDB: 2013/12
Experimental Method:
x-ray diffraction
Resolution: 2.61  Å
Source Organism:
Similar Structures:
Biological Unit for 4MDK: dimeric; determined by author
Molecular Components in 4MDK
Label Count Molecule
Proteins (2 molecules)
1
Ubiquitin-conjugating Enzyme E2 R1(Gene symbol: CDC34)
Molecule annotation
1
Ubiquitin(Gene symbol: UBC)
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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