4ONL

Crystal structure of human Mms2/Ubc13_D81N, R85S, A122V, N123P

4ONL の概要

• エントリーDOI: 10.2210/pdb4onl/pdb
• 関連するPDBエントリー: 4ONM 4ONN
• 分子名称: Ubiquitin-conjugating enzyme E2 variant 2, Ubiquitin-conjugating enzyme E2 N (3 entities in total)
• 機能のキーワード: ubc13, mms2, e2, ubiquitin conjugating enzyme, ligase
• 由来する生物種: Homo sapiens (human); 詳細
• 細胞内の位置: Nucleus : P61088
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 35048.19

構造登録者

Hodge, C.D.,Edwards, R.A.,Glover, J.N.M. (登録日: 2014-01-28, 公開日: 2015-05-06, 最終更新日: 2024-02-28)

主引用文献

Hodge, C.D.,Edwards, R.A.,Markin, C.J.,McDonald, D.,Pulvino, M.,Huen, M.S.,Zhao, J.,Spyracopoulos, L.,Hendzel, M.J.,Glover, J.N.
Covalent Inhibition of Ubc13 Affects Ubiquitin Signaling and Reveals Active Site Elements Important for Targeting.
Acs Chem.Biol., 10:1718-1728, 2015

PubMed Abstract: Ubc13 is an E2 ubiquitin conjugating enzyme that functions in nuclear DNA damage signaling and cytoplasmic NF-κB signaling. Here, we present the structures of complexes of Ubc13 with two inhibitors, NSC697923 and BAY 11-7082, which inhibit DNA damage and NF-κB 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-κB 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.

PubMed: 25909880
DOI: 10.1021/acschembio.5b00222

実験手法

X-RAY DIFFRACTION (1.35 Å)