› 6kzd

X-ray diffraction
1.71Å resolution

Crystal structure of TRKc in complex with 3-((6-(4-aminophenyl)imidazo[1,2-a]pyrazin-3-yl)ethynyl)- N-(3-isopropyl-5-((4-methylpiperazin-1-yl)methyl)phenyl)-2- methylbenzamide

Released:
DOI: 10.2210/pdb6kzd/pdb
PDB entry 6kzd coloured by chain, front view.
PDB entry 6kzd coloured by chain, side view.
PDB entry 6kzd coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Design, synthesis and biological evaluation of 3-(imidazo[1,2-a]pyrazin-3-ylethynyl)-2-methylbenzamides as potent and selective pan-tropomyosin receptor kinase (TRK) inhibitors.
Cui S, Wang Y, Wang Y, Tang X, Ren X, Zhang L, Xu Y, Zhang Z, Zhang ZM, Lu X, Ding K
Eur J Med Chem 179 470-482 (2019)
PMID: 31271959

Function and Biology Details

Reaction catalysed: 
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-172460 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
NT-3 growth factor receptor Chain: A
Molecule details ›
Chain: A
Length: 312 amino acids
Theoretical weight: 35.83 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli
UniProt:
  • Canonical: Q16288 (Residues: 528-839; Coverage: 39%)
Gene names: NTRK3, TRKC
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

2 bound ligands:
Ligand DZ6 1 x DZ6
Ligand PO4 1 x PO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: SSRF BEAMLINE BL17U1
Spacegroup: P212121
Unit cell:
a: 51.695Å b: 54.569Å c: 108.842Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.16 0.159 0.184
Expression system: Escherichia coli

Quick links

Citations

1 review citation

Synthetic Heterocyclic Derivatives as Kinase Inhibitors Tested for the Treatment of Neuroblastoma.
Musumeci et al. (2021)
1 other article

4 mentions without citation

Selective type II TRK inhibitors overcome xDFG mutation mediated acquired resistance to the second-generation inhibitors selitrectinib and repotrectinib.
Xiang et al. (2024)
3 more