4ONN: Crystal structure of human Mms2/Ubc13 - BAY 11-7082

Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-kappaB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-kappaB signaling in human cells. NSC697923 and BAY 11-7082 both inhibit Ubc13 by covalent adduct formation through a Michael addition at the Ubc13 active site cysteine. The resulting adducts of both compounds exploit a binding groove unique to Ubc13. We developed a Ubc13 mutant which resists NSC697923 inhibition and, using this mutant, we show that the inhibition of cellular DNA damage and NF-kappaB signaling by NSC697923 is largely due to specific Ubc13 inhibition. We propose that unique structural features near the Ubc13 active site could provide a basis for the rational development and design of specific Ubc13 inhibitors.
PDB ID: 4ONNDownload
MMDB ID: 128999
PDB Deposition Date: 2014/1/28
Updated in MMDB: 2017/12
Experimental Method:
x-ray diffraction
Resolution: 1.5  Å
Source Organism:
Similar Structures:
Biological Unit for 4ONN: dimeric; determined by author and by software (PISA)
Molecular Components in 4ONN
Label Count Molecule
Proteins (2 molecules)
Ubiquitin-conjugating Enzyme E2 Variant 2(Gene symbol: UBE2V2)
Molecule annotation
Ubiquitin-conjugating Enzyme E2 N(Gene symbol: UBE2N)
Molecule annotation
Chemicals (4 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB