6SC6

dAb3/HOIP-RBR apo structure

Summary for 6SC6

• Entry DOI: 10.2210/pdb6sc6/pdb
• Descriptor: E3 ubiquitin-protein ligase RNF31, Single domain antibody, ZINC ION, ... (6 entities in total)
• Functional Keywords: human single domain antibody, hoip, rbr, ligase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 70468.03

Authors

Tsai, Y.-C.I.,House, D.,Rittinger, K. (deposition date: 2019-07-23, release date: 2019-11-27, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.25 Å)