› 8j5x

X-ray diffraction
2.09Å resolution

The crystal structure of TrkA(G595R) kinase in complex with N-(3-cyclopropyl-5-((4-methylpiperazin-1-yl)methyl)phenyl)-4^6-methyl-14-oxo-5-oxa-13-aza-1(3,6)-imidazo[1,2-b]pyridazina-4(1,3)-benzenacyclotetradecaphan-2-yne-4^5-carboxamide

Released:
DOI: 10.2210/pdb8j5x/pdb
PDB entry 8j5x coloured by chain, front view.
PDB entry 8j5x coloured by chain, side view.
PDB entry 8j5x 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: 34.01 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 A4U 1 x A4U
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: CAMD BEAMLINE GCPCC
Spacegroup: P3112
Unit cell:
a: 51.843Å b: 51.843Å c: 229.331Å
α: 90° β: 90° γ: 120°
R-values:
R R work R free
0.184 0.18 0.22
Expression system: Baculovirus expression vector pFastBac1-HM

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