6SC5

dAb3/HOIP-RBR-Ligand2

6SC5 の概要

• エントリーDOI: 10.2210/pdb6sc5/pdb
• 分子名称: E3 ubiquitin-protein ligase RNF31, Single domain antibody, methyl 4-[(2-oxidanylidene-5,6,7,8-tetrahydro-1~{H}-quinolin-3-yl)carbonylamino]but-3-enoate, ... (7 entities in total)
• 機能のキーワード: human single domain antibody, hoip, rbr, inhibitor, ligase
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 70626.82

構造登録者

Tsai, Y.-C.I.,Johansson, H.,House, D.,Rittinger, K. (登録日: 2019-07-23, 公開日: 2019-11-27, 最終更新日: 2024-11-13)

主引用文献

Tsai, Y.I.,Johansson, H.,Dixon, D.,Martin, S.,Chung, C.W.,Clarkson, J.,House, D.,Rittinger, K.
Single-Domain Antibodies as Crystallization Chaperones to Enable Structure-Based Inhibitor Development for RBR E3 Ubiquitin Ligases.
Cell Chem Biol, 27:83-, 2020

PubMed Abstract: Protein ubiquitination plays a key role in the regulation of cellular processes, and misregulation of the ubiquitin system is linked to many diseases. So far, development of tool compounds that target enzymes of the ubiquitin system has been slow and only a few specific inhibitors are available. Here, we report the selection of single-domain antibodies (single-dAbs) based on a human scaffold that recognize the catalytic domain of HOIP, a subunit of the multi-component E3 LUBAC and member of the RBR family of E3 ligases. Some of these dAbs affect ligase activity and provide mechanistic insight into the ubiquitin transfer mechanism of different E2-conjugating enzymes. Furthermore, we show that the co-crystal structure of a HOIP RBR/dAb complex serves as a robust platform for soaking of ligands that target the active site cysteine of HOIP, thereby providing easy access to structure-based ligand design for this important class of E3 ligases.

PubMed: 31813847
DOI: 10.1016/j.chembiol.2019.11.007

実験手法

X-RAY DIFFRACTION (2.1 Å)