8EDH: Serine/threonine-protein kinase WNK3

Identification of a class of WNK isoform-specific inhibitors through high-throughput screening. Determined by X-ray diffraction at 3.11 Å resolution. Released 1 Mar 2023.

Method: X-ray diffraction
Resolution: 3.11 Å
Organism: Homo sapiens
Chains: 2
Atoms: 4,310
Mol. weight: 67.63 kDa
Ligands: WGK
Released: 1 Mar 2023

Explore 8EDH in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

8EDH contains 30 α-helices and 24 β-strands across 2 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: 16 helices, 13 β-strands

Element	Residues	Length	Sheet
β-strand	139-140	2	1
β-strand	146-154	9	1
β-strand	159-166	8	1
β-strand	172-179	8	1
α-helix	180-182	3
α-helix	185-187	3
α-helix	188-199	12
β-strand	203	1	2
β-strand	206	1	2
β-strand	209-213	5	1
β-strand	216-217	2	3
β-strand	220-221	2	3
β-strand	222-228	7	1
β-strand	234	1	2
α-helix	235-242	8
α-helix	247-265	19
α-helix	270-272	3
α-helix	278-280	3
β-strand	281-283	3	2
β-strand	290-292	3	2
α-helix	296-298	3
α-helix	318-320	3
α-helix	327-343	17
α-helix	354-362	9
α-helix	365-367	3
α-helix	368-372	5
α-helix	376-385	10
α-helix	390-392	3
α-helix	396-400	5

Chain C: 14 helices, 11 β-strands

Element	Residues	Length	Sheet
β-strand	139-140	2	4
β-strand	146-154	9	4
β-strand	161-166	6	4
β-strand	172-178	7	4
α-helix	179-180	2
α-helix	185-199	15
β-strand	203	1	5
β-strand	206	1	5
β-strand	209-217	9	4
β-strand	220-228	9	4
β-strand	234	1	5
α-helix	235-241	7
α-helix	247-265	19
α-helix	270-271	2
α-helix	278-280	3
β-strand	281-283	3	5
β-strand	290-292	3	5
α-helix	296-299	4
α-helix	318-321	4
α-helix	327-343	17
α-helix	354-362	9
α-helix	368-372	5
α-helix	376-385	10
α-helix	390-392	3
α-helix	396-401	6

Molecules and chains

Molecule	Chains	Type	Length	Organism	UniProt
Serine/threonine-protein kinase WNK3	A, C	protein	292	Homo sapiens	Q9BYP7 (AlphaFold model)

Sequence of entity 1 (A, C), FASTA

>8EDH_1 Serine/threonine-protein kinase WNK3 (chains A, C)
KDCFKEKNEKEMEEEAEMKAVATSPSGRFLKFDIELGRGAFKTVYKGLDTETWVEVAWCE
LQDRKLTKAEQQRFKEEAEMLKGLQHPNIVRFYDSWESILKGKKCIVLVTELMTSGTLKT
YLKRFKVMKPKVLRSWCRQILKGLQFLHTRTPPIIHRDLKCDNIFITGPTGSVKIGDLGL
ATLMRTSFAKAVIGTPEFMAPEMYEEHYDESVDVYAFGMCMLEMATSEYPYSECQNAAQI
YRKVTSGIKPASFNKVTDPEVKEIIEGCIRQNKSERLSIRDLLNHAFFAEDT

Ligands and cofactors

ID	Name	Formula	Copies
WGK	ethyl 1-(5,7-dimethoxy-4-methylquinolin-2-yl)piperidine-4-carboxylate	C20 H26 N2 O4	1

Primary citation

Identification of a Class of WNK Isoform-Specific Inhibitors Through High-Throughput Screening. Chlebowicz, J., Akella, R., Humphreys, J.M. et al. Drug Des Devel Ther (2023) 17:93-105. DOI 10.2147/DDDT.S389461 · PubMed

Other PDB entries of the same protein (UniProt Q9BYP7 (AlphaFold model), which also has an AlphaFold model), best resolution first:

5O1V 1.72 Å, Crystal structure of WNK3 kinase domain in a monophosphorylated apo state (A-loop swapped)
5O2B 2.04 Å, Crystal structure of WNK3 kinase domain in a diphosphorylated state and in a complex…
5O21 2.06 Å, Crystal structure of WNK3 kinase domain in a monophosphorylated state with chloride…
5O23 2.25 Å, Crystal structure of WNK3 kinase domain in a monophosphorylated apo state
5O26 2.38 Å, Crystal structure of WNK3 kinase domain in a diphosphorylated state and in complex with…
5O2C 2.4 Å, Crystal structure of WNK3 kinase and CCT1 didomain in a unphosphorylated state
5NKP 2.8 Å, Crystal structure of the human KLHL3 Kelch domain in complex with a WNK3 peptide
9D7Q 3.3 Å, Water and chloride as allosteric inhibitors in WNK kinase osmosensing

Browse structure collections

About this viewer

MolViewer shows 8EDH directly in your browser with nothing to install. Switch between cartoon, ball-and-stick, spacefill and surface views, color by chain, secondary structure or B-factor, measure distances, angles and dihedrals, and share or embed the view.