› 7k7l

X-ray diffraction
2.54Å resolution

Structure of a hit for G Protein Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure

Released:
DOI: 10.2210/pdb7k7l/pdb
PDB entry 7k7l coloured by chain, front view.
PDB entry 7k7l coloured by chain, side view.
PDB entry 7k7l coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Hit-to-lead optimization and discovery of a potent, and orally bioavailable G protein coupled receptor kinase 2 (GRK2) inhibitor.
Xu G, Gaul MD, Liu Z, DesJarlais RL, Qi J, Wang W, Krosky D, Petrounia I, Milligan CM, Hermans A, Lu HR, Huang DZ, Xu JZ, Spurlino JC
Bioorg Med Chem Lett 30 127602 (2020)
PMID: 33038544

Function and Biology Details

Reaction catalysed: 
ATP + [beta-adrenergic receptor] = ADP + [beta-adrenergic receptor] phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
PDBe Complex ID:
PDB-CPX-150374 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
Beta-adrenergic receptor kinase 1 Chain: A
Molecule details ›
Chain: A
Length: 640 amino acids
Theoretical weight: 74.55 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: P25098 (Residues: 30-668; Coverage: 93%)
Gene names: ADRBK1, BARK, BARK1, GRK2
Sequence domains:
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 Chain: B
Molecule details ›
Chain: B
Length: 339 amino acids
Theoretical weight: 37.29 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: P62873 (Residues: 2-340; Coverage: 100%)
Gene name: GNB1
Sequence domains: WD domain, G-beta repeat
Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 Chain: G
Molecule details ›
Chain: G
Length: 59 amino acids
Theoretical weight: 6.52 KDa
Source organism: Homo sapiens
Expression system: unidentified baculovirus
UniProt:
  • Canonical: P59768 (Residues: 6-64; Coverage: 83%)
Gene name: GNG2
Sequence domains: GGL domain

Ligands and Environments

2 bound ligands:
Ligand MG 1 x MG
Ligand W4D 1 x W4D
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: APS BEAMLINE 17-ID
Spacegroup: C2
Unit cell:
a: 194.398Å b: 70.766Å c: 111.236Å
α: 90° β: 110.58° γ: 90°
R-values:
R R work R free
0.203 0.201 0.244
Expression system: unidentified baculovirus

Quick links

Citations

2 citation in other articles

A bead-based GPCR phosphorylation immunoassay for high-throughput ligand profiling and GRK inhibitor screening.
Kaufmann et al. (2022)
1 more