Human Kelch-like ECH Associated Protein 1 (KEAP1)The content of this page was edited by SGC and admin and matteoferla on the 2019-10-07 15:59:03.280099.
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KEAP1 is a highly redox-sensitive member of the BTB-Kelch family that assembles with the CUL3 protein to form a Cullin-RING E3 ligase complex for the degradation of NRF2. Oxidative stress disables KEAP1 allowing NRF2 protein levels to accumulate for the transactivation of critical stress response genes. Consequently, the KEAP1-NRF2 system is a highly attractive target for the development of protein-protein interaction inhibitors that will stabilise NRF2 for therapeutic effect in conditions of neurodegeneration and inflammation. As part of this TEP we have solved the first crystal structure of a KEAP1-CUL3 complex as well as a structure of the apo-Kelch domain suitable for small molecule soaking. We further established a selectivity assay panel of 17 human Kelch domain-containing proteins and have shown that non-covalent KEAP1 inhibitors from the literature are highly selective for KEAP1. This protein panel offers a resource for future work on KEAP1 as well as 16 other human Kelch proteins.
Structures available in TEP:
- Structure of KEAP1 BTB-3-box in complex with CUL3NTD (PDB:5NLB ): ,
- Structure of apo-Kelch domain of KEAP1 (PDB:6ROG ): ,
- Structure of apo-Kelch domain of KLHL2 (PDB:2XN4 ): ,
- Structure of the KLHL2 Kelch domain with WNK4 peptide (PDB:4CHB ): ,
- Structure of the KLHL3 Kelch domain with WNK4 peptide (PDB:4CH9 ): ,
- Structure of the KLHL3 Kelch domain with WNK3 peptide (PDB:5NKP ): ,
- Structure of the apo-Kelch domain of KLHL7 (PDB:3II7 ): ,
- Structure of the BTB-BACK domains of KLHL11 (PDB:3I3N ): ,
- Structure of the KLHL11 BTB-BACK domains with CUL3NTD (PDB:4AP2 ): ,
- Structure of the KLHL11 BTB-BACK with CUL3NTDΔN22 (PDB:4APF ): ,
- Structure of the apo-Kelch domain of KLHL12 (PDB:2VPJ ): ,
- Structure of the apo-Kelch domain of KLHL17 (PDB:6HRL ): ,
- Structure of the KLHL20 Kelch domain with DAPK1 peptide (PDB:6GY5 ): ,
- Structure of the apo-Kelch domain of KLHL40 (KBTBD5) (PDB:4ASC ): ,