6V6Z

Crystal structure of N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine bound to human Keap1 Kelch domain

6V6Z の概要

• エントリーDOI: 10.2210/pdb6v6z/pdb
• 分子名称: Kelch-like ECH-associated protein 1, FORMIC ACID, N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine, ... (7 entities in total)
• 機能のキーワード: protein-protein interaction inhibitor, keap1, nrf2 activator, protein binding-inhibitor complex, protein binding/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 132025.88

構造登録者

Lazzara, P.R.,David, B.P.,Ankireddy, A.,Richardson, B.G.,Dye, K.,Ratia, K.M.,Reddy, S.P.,Moore, T.W. (登録日: 2019-12-06, 公開日: 2020-04-29, 最終更新日: 2023-10-11)

主引用文献

Lazzara, P.R.,Jain, A.D.,Maldonado, A.C.,Richardson, B.,Skowron, K.J.,David, B.P.,Siddiqui, Z.,Ratia, K.M.,Moore, T.W.
Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors.
Acs Med.Chem.Lett., 11:521-527, 2020

PubMed Abstract: The oxidative stress response, gated by the protein-protein interaction of KEAP1 and NRF2, has garnered significant interest in the past decade. Misregulation in this pathway has been implicated in disease states such as multiple sclerosis, rheumatoid arthritis, and diabetic chronic wounds. Many of the known activators of NRF2 are electrophilic in nature and may operate through several biological pathways rather than solely through the activation of the oxidative stress response. Recently, our lab has reported a nonelectrophilic, monoacidic, naphthalene-based NRF2 activator which exhibited good potency . Herein, we report a detailed structure-activity relationship of naphthalene-based NRF2 activators, an X-ray crystal structure of our monoacidic KEAP1 inhibitor, and identification of an underexplored area of the NRF2 binding pocket of KEAP1.

PubMed: 32292559
DOI: 10.1021/acsmedchemlett.9b00631

実験手法

X-RAY DIFFRACTION (1.6 Å)