5DAF

Crystal Structure of Human KEAP1 BTB Domain in Complex with Small Molecule TX64063

Summary for 5DAF

• Entry DOI: 10.2210/pdb5daf/pdb
• Related: 5DAD
• Descriptor: Kelch-like ECH-associated protein 1, (5aS,6S,9aS)-7-hydroxy-2,6,9a-trimethyl-3-(pyridin-3-yl)-4,5,5a,6,9,9a-hexahydro-2H-benzo[g]indazole-8-carbonitrile (3 entities in total)
• Functional Keywords: keap1, trascription regulation, btb domain, cysteine modification, c1-(r)-cys151 adduct, transcription
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: Q14145
• Total number of polymer chains: 1
• Total formula weight: 15929.37

Authors

Huerta, C.,Jiang, X.,Trevino, I.,Bender, C.F.,Swinger, K.K.,Stoll, V.S.,Ferguson, D.A.,Thomas, P.J.,Probst, B.,Dulubova, I.,Visnick, M.,Wigley, W.C. (deposition date: 2015-08-19, release date: 2016-08-10, Last modification date: 2024-11-20)

Primary citation

Huerta, C.,Jiang, X.,Trevino, I.,Bender, C.F.,Ferguson, D.A.,Probst, B.,Swinger, K.K.,Stoll, V.S.,Thomas, P.J.,Dulubova, I.,Visnick, M.,Wigley, W.C.
Characterization of novel small-molecule NRF2 activators: Structural and biochemical validation of stereospecific KEAP1 binding.
Biochim.Biophys.Acta, 1860:2537-2552, 2016

PubMed Abstract: Semi-synthetic oleanane triterpenoid antioxidant inflammation modulators (tpAIMs) are small molecules that interact with KEAP1 cysteine residue 151 (C151) and activate NRF2. Exploration of the structure-activity relationship between the tpAIMs and KEAP1 is limited by the predominantly hydrocarbon nature of the oleanane triterpenoid pentacyclic ring structure. Therefore, we used novel, chemically-tractable, synthetic antioxidant inflammation modulators (sAIMs) to probe the stereoselectivity of the ligand-protein interaction.

PubMed: 27474998
DOI: 10.1016/j.bbagen.2016.07.026

Experimental method

X-RAY DIFFRACTION (2.37 Å)