Projects per year
Reproducible structural information and detailed validation of protein-ligand interactions aid drug discovery. However, the isolated TrkAIg2 domain crystallizes as a β-strand-swapped dimer in the absence of NGF, occluding the binding surface. Here we report the design and structural validation by nuclear magnetic resonance spectroscopy of the first stable, biologically active construct of the TrkAIg2 domain for binding-site confirmation. Our structure closely mimics the wild-type fold of TrkAIg2 in complex with NGF (1WWW.pdb)
and the 1H-15N correlation spectra confirm that both NGF and a competing small molecule, interact at the known binding interface in solution.
- BCS and TECS CDTs
- TrkA, TrkAIg2, drug discovery, NMR construct, pain, Alzheimer’s
Allen-Birt, S. J. A.
1/03/10 → 1/09/12