6V6Z: Kelch-like ECH-associated protein 1

Crystal structure of N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen-1-yl)glycine bound to human Keap1 Kelch domain. Determined by X-ray diffraction at 1.6 Å resolution. Released 29 Apr 2020.

Method: X-ray diffraction
Resolution: 1.6 Å
Organism: Homo sapiens
Chains: 4
Atoms: 10,213
Mol. weight: 132.03 kDa
Ligands: Q5Y, DTD, DTT
Released: 29 Apr 2020

Explore 6V6Z in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

6V6Z contains 20 α-helices and 160 β-strands across 4 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 5 helices, 40 β-strands

Element	Residues	Length	Sheet
β-strand	328-331	4	1
β-strand	334-335	2	2
β-strand	337-338	2	2
β-strand	342-346	5	1
β-strand	351-354	4	1
α-helix	356-358	3
β-strand	363	1	3
β-strand	366-370	5	4
β-strand	373-377	5	4
β-strand	380-383	4	3
β-strand	386-389	4	3
β-strand	393-397	5	4
β-strand	402-405	4	4
α-helix	407-409	3
β-strand	414	1	5
β-strand	417-421	5	6
β-strand	424-428	5	6
β-strand	431-432	2	5
β-strand	435-436	2	5
β-strand	440-444	5	6
β-strand	449-453	5	6
α-helix	454-456	3
β-strand	461	1	7
β-strand	464-468	5	7
β-strand	471-478	8	7
β-strand	483-491	9	7
β-strand	496-499	4	7
α-helix	501-503	3
β-strand	508	1	8
β-strand	511-515	5	9
β-strand	518-522	5	9
β-strand	525	1	8
β-strand	530	1	8
β-strand	534-538	5	9
β-strand	543-546	4	9
α-helix	548-550	3
β-strand	555	1	10
β-strand	558-562	5	11
β-strand	565-569	5	11
β-strand	572	1	10
β-strand	577	1	10
β-strand	580-585	6	11
β-strand	590-596	7	11
β-strand	602	1	2
β-strand	605-608	4	1

Chains B, C and D: 5 helices, 40 β-strands

Element	Residues	Length	Sheet
β-strand	328-331	4	12
β-strand	334-335	2	13
β-strand	337-338	2	13
β-strand	342-346	5	12
β-strand	351-354	4	12
α-helix	356-358	3
β-strand	363	1	14
β-strand	366-370	5	15
β-strand	373-377	5	15
β-strand	380-383	4	14
β-strand	386-389	4	14
β-strand	393-397	5	15
β-strand	402-405	4	15
α-helix	407-409	3
β-strand	414	1	16
β-strand	417-421	5	17
β-strand	424-428	5	17
β-strand	431-432	2	16
β-strand	435-436	2	16
β-strand	440-444	5	17
β-strand	449-452	4	17
α-helix	454-456	3
β-strand	461	1	18
β-strand	464-468	5	18
β-strand	471-478	8	18
β-strand	483-491	9	18
β-strand	496-499	4	18
α-helix	501-503	3
β-strand	508	1	19
β-strand	511-515	5	20
β-strand	518-522	5	20
β-strand	525	1	19
β-strand	530	1	19
β-strand	534-538	5	20
β-strand	543-546	4	20
α-helix	548-550	3
β-strand	555	1	21
β-strand	558-562	5	22
β-strand	565-569	5	22
β-strand	572	1	21
β-strand	577	1	21
β-strand	580-585	6	22
β-strand	590-596	7	22
β-strand	602	1	13
β-strand	605-608	4	12

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Kelch-like ECH-associated protein 1	A, B, C, D	protein	290	Homo sapiens	Q14145 (AlphaFold model)

Sequence of entity 1 (A, B, C, D), FASTA

>6V6Z_1 Kelch-like ECH-associated protein 1 (chains A, B, C, D)
SAPKVGRLIYTAGGYFRQSLSYLEAYNPSDGTWLRLADLQVPRSGLAGCVVGGLLYAVGG
RNNSPDGNTDSSALDCYNPMTNQWSPCAPMSVPRNRIGVGVIDGHIYAVGGSHGCIHHNS
VERYEPERDEWHLVAPMLTRRIGVGVAVLNRLLYAVGGFDGTNRLNSAECYYPERNEWRM
ITAMNTIRSGAGVCVLHNCIYAAGGYDGQDQLNSVERYDVATATWTFVAPMKHRRSALGI
TVHQGRIYVLGGYDGHTFLDSVECYDPDTDTWSEVTRMTSGRSGVGVAVT

Ligands and cofactors

ID	Name	Formula	Copies
Q5Y	N-[(4-methoxyphenyl)sulfonyl]-N-(4-{[(4-methoxyphenyl)sulfonyl]amino}naphthalen…	C26 H24 N2 O8 S2	4
DTD	Dithiane diol	C4 H8 O2 S2	1
DTT	2,3-dihydroxy-1,4-dithiobutane	C4 H10 O2 S2	1

Water and common crystallization additives (FMT, NA) are not listed.

Primary citation

Synthesis and Evaluation of Noncovalent Naphthalene-Based KEAP1-NRF2 Inhibitors. Lazzara, P.R., Jain, A.D., Maldonado, A.C. et al. ACS Med Chem Lett (2020) 11:521-527. DOI 10.1021/acsmedchemlett.9b00631 · PubMed

Other PDB entries of the same protein (UniProt Q14145 (AlphaFold model), which also has an AlphaFold model), best resolution first:

8XGK 1.32 Å, Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2…
1ZGK 1.35 Å, 1.35 angstrom structure of the Kelch domain of Keap1
8XGV 1.42 Å, Optimization Efforts for Identification of Novel Highly Potent Keap1-Nrf2…
6TYM 1.42 Å, KEAP1 Kelch domain in complex with Compound 9
9KVW 1.44 Å, Crystal Structures of Keap1-compound complexes
8IXS 1.48 Å, Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1/Nrf2 PPI Inhibitor for…
2FLU 1.5 Å, Crystal Structure of the Kelch-Neh2 Complex
8IVR 1.5 Å, Methyl and Fluorine Effects in Novel Orally Bioavailable Keap1/Nrf2 PPI Inhibitor for…
9R1Z 1.5 Å, Keap1 - inhibitor complex - 3
8PKW 1.54 Å, Kelch domain of KEAP1 in complex with a ortho-dimethylbenzene linked cyclic peptide 5…
8PKV 1.55 Å, Kelch domain of KEAP1 in complex with a ortho-dimethylbenzene linked cyclic peptide 4…
9M24 1.57 Å, Crystal Structure of kelch domain of human KEAP1 in complex with CH7450924

Browse structure collections

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