› 8j63

X-ray diffraction
3Å resolution

The crystal structure of TrkA kinase in complex with 4^6-methyl-N-(3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl)-11-oxo-5-oxa-10,14-diaza-1(3,6)-imidazo[1,2-b]pyridazina-4(1,3)-benzenacyclotetradecaphan-2-yne-4^5-carboxamide

Released:
DOI: 10.2210/pdb8j63/pdb
PDB entry 8j63 coloured by chain, front view.
PDB entry 8j63 coloured by chain, side view.
PDB entry 8j63 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structure-Based Optimization of the Third Generation Type II Macrocycle TRK Inhibitors with Improved Activity against Solvent-Front, xDFG, and Gatekeeper Mutations.
Wang Z, Wang J, Wang Y, Xiang S, Zhou H, Song S, Song X, Tu Z, Zhou Y, Ding K, Zhang ZM, Zhang Z, Lu X
J Med Chem (2023)
PMID: 37676745

Function and Biology Details

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

Structure analysis Details

Assembly composition:
monomeric (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-138088 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
High affinity nerve growth factor receptor Chain: A
Molecule details ›
Chain: A
Length: 299 amino acids
Theoretical weight: 33.91 KDa
Source organism: Homo sapiens
Expression system: Baculovirus expression vector pFastBac1-HM
UniProt:
  • Canonical: P04629 (Residues: 498-796; Coverage: 39%)
Gene names: MTC, NTRK1, TRK, TRKA
Sequence domains: Protein tyrosine and serine/threonine kinase

Ligands and Environments

1 bound ligand:
Ligand A6X 1 x A6X
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CAMD BEAMLINE GCPCC
Spacegroup: P3112
Unit cell:
a: 52.125Å b: 52.125Å c: 228.168Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.233 0.226 0.289
Expression system: Baculovirus expression vector pFastBac1-HM

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