6V6Z
Crystal structure of N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine bound to human Keap1 Kelch domain
Summary for 6V6Z
| Entry DOI | 10.2210/pdb6v6z/pdb |
| Descriptor | 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) |
| Functional Keywords | protein-protein interaction inhibitor, keap1, nrf2 activator, protein binding-inhibitor complex, protein binding/inhibitor |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 4 |
| Total formula weight | 132025.88 |
| Authors | Lazzara, P.R.,David, B.P.,Ankireddy, A.,Richardson, B.G.,Dye, K.,Ratia, K.M.,Reddy, S.P.,Moore, T.W. (deposition date: 2019-12-06, release date: 2020-04-29, Last modification date: 2023-10-11) |
| Primary citation | 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 Cited by 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: 32292559DOI: 10.1021/acsmedchemlett.9b00631 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.6 Å) |
Structure validation
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