› 5we8

X-ray diffraction
2.01Å resolution

Crystal structure of WNK1 in complex with N-{(3R)-1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl}-2-(3-methoxyphenyl)-N-methylquinoline-4-carboxamide (compound 8)

Released:
DOI: 10.2210/pdb5we8/pdb
PDB entry 5we8 coloured by chain, front view.
PDB entry 5we8 coloured by chain, side view.
PDB entry 5we8 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Optimization of Allosteric With-No-Lysine (WNK) Kinase Inhibitors and Efficacy in Rodent Hypertension Models.
Yamada K, Levell J, Yoon T, Kohls D, Yowe D, Rigel DF, Imase H, Yuan J, Yasoshima K, DiPetrillo K, Monovich L, Xu L, Zhu M, Kato M, Jain M, Idamakanti N, Taslimi P, Kawanami T, Argikar UA, Kunjathoor V, Xie X, Yagi YI, Iwaki Y, Robinson Z, Park HM
J Med Chem 60 7099-7107 (2017)
PMID: 28771350

Function and Biology Details

Reaction catalysed: 
ATP + a protein = ADP + a phosphoprotein
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-190604 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Serine/threonine-protein kinase WNK1 Chains: A, B
Molecule details ›
Chains: A, B
Length: 279 amino acids
Theoretical weight: 31.89 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q9H4A3 (Residues: 206-483; Coverage: 12%)
Gene names: HSN2, KDP, KIAA0344, PRKWNK1, WNK1
Sequence domains: Protein kinase domain
Structure domains:

Ligands and Environments

3 bound ligands:
Ligand MN 2 x MN
Ligand ANP 2 x ANP
Ligand A7Y 2 x A7Y
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SLS BEAMLINE X10SA
Spacegroup: C2
Unit cell:
a: 83.102Å b: 105.235Å c: 70.105Å
α: 90° β: 117.28° γ: 90°
R-values:
R R work R free
0.205 0.202 0.247
Expression system: Escherichia coli

Quick links

Citations

8 review citations

WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension.
Brown et al. (2021)
7 more