› 6vhg

X-ray diffraction
2.3Å resolution

Crystal structure of phosphorylated RET tyrosine kinase domain complexed with a pyrazolo[1,5-a]pyrimidine inhibitor

Released:
DOI: 10.2210/pdb6vhg/pdb
PDB entry 6vhg coloured by chain, front view.
PDB entry 6vhg coloured by chain, side view.
PDB entry 6vhg coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Efficacy and Tolerability of Pyrazolo[1,5-a]pyrimidine RET Kinase Inhibitors for the Treatment of Lung Adenocarcinoma.
Mathison CJN, Chianelli D, Rucker PV, Nelson J, Roland J, Huang Z, Yang Y, Jiang J, Xie YF, Epple R, Bursulaya B, Lee C, Gao MY, Shaffer J, Briones S, Sarkisova Y, Galkin A, Li L, Li N, Li C, Hua S, Kasibhatla S, Kinyamu-Akunda J, Kikkawa R, Molteni V, Tellew JE
ACS Med Chem Lett 11 558-565 (2020)
PMID: 32292564

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
  • not assigned
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-139853 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Soluble RET kinase fragment Chain: A
Molecule details ›
Chain: A
Length: 311 amino acids
Theoretical weight: 35.53 KDa
Source organism: Homo sapiens
Expression system: Spodoptera frugiperda
UniProt:
  • Canonical: P07949 (Residues: 705-1013; Coverage: 29%)
Gene names: CDHF12, CDHR16, PTC, RET
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

4 bound ligands:
Ligand QX1 1 x QX1
Ligand SO4 4 x SO4
Ligand CL 2 x CL
Ligand ACT 1 x ACT
1 modified residue:
Ligand PTR 2 x PTR

Experiments and Validation Details

Entry percentile scores
X-ray source: ALS BEAMLINE 5.0.3
Spacegroup: P6322
Unit cell:
a: 97.815Å b: 97.815Å c: 143.963Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.204 0.203 0.238
Expression system: Spodoptera frugiperda

Quick links

Citations

1 review citation

Functional Pyrazolo[1,5-a]pyrimidines: Current Approaches in Synthetic Transformations and Uses As an Antitumor Scaffold.
Arias-Gómez et al. (2021)
5 other articles

2 mentions without citation

Experimental and Theoretical Insights on Chemopreventive Effect of the Liposomal Thymoquinone Against Benzo[a]pyrene-Induced Lung Cancer in Swiss Albino Mice.
Khan et al. (2022)
1 more