3ZGD

crystal structure of a KEAP1 mutant

3ZGD の概要

• エントリーDOI: 10.2210/pdb3zgd/pdb
• 関連するPDBエントリー: 3ZGC
• 分子名称: KELCH-LIKE ECH-ASSOCIATED PROTEIN 1, ACETATE ION, SODIUM ION, ... (4 entities in total)
• 機能のキーワード: transcription, crystal contact engineering
• 由来する生物種: HOMO SAPIENS (HUMAN)
• 細胞内の位置: Cytoplasm: Q14145
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 68295.13

構造登録者

Hoerer, S.,Reinert, D.,Ostmann, K.,Hoevels, Y.,Nar, H. (登録日: 2012-12-17, 公開日: 2013-06-12, 最終更新日: 2023-12-20)

主引用文献

Horer, S.,Reinert, D.,Ostmann, K.,Hoevels, Y.,Nar, H.
Crystal-Contact Engineering to Obtain a Crystal Form of the Kelch Domain of Human Keap1 Suitable for Ligand-Soaking Experiments.
Acta Crystallogr.,Sect.F, 69:592-, 2013

PubMed Abstract: Keap1 is a substrate adaptor protein for a Cul3-dependent ubiquitin ligase complex and plays an important role in the cellular response to oxidative stress. It binds Nrf2 with its Kelch domain and thus triggers the ubiquitinylation and degradation of Nrf2. Oxidative stress prevents the degradation of Nrf2 and leads to the activation of cytoprotective genes. Therefore, Keap1 is an attractive drug target in inflammatory diseases. The support of a medicinal chemistry effort by structural research requires a robust crystallization system in which the crystals are preferably suited for performing soaking experiments. This facilitates the generation of protein-ligand complexes in a routine and high-throughput manner. The structure of human Keap1 has been described previously. In this crystal form, however, the binding site for Nrf2 was blocked by a crystal contact. This interaction was analysed and mutations were introduced to disrupt this crystal contact. One double mutation (E540A/E542A) crystallized in a new crystal form in which the binding site for Nrf2 was not blocked and was accessible to small-molecule ligands. The crystal structures of the apo form of the mutated Keap1 Kelch domain (1.98 Å resolution) and of the complex with an Nrf2-derived peptide obtained by soaking (2.20 Å resolution) are reported.

PubMed: 23722832
DOI: 10.1107/S174430911301124X

実験手法

X-RAY DIFFRACTION (1.98 Å)