4CRP: Solution structure of a TrkAIg2 domain construct for use in drug discovery

Citation:
Abstract
The tyrosine kinase A (TrkA) receptor is a validated therapeutic intervention point for a wide range of conditions. TrkA activation by nerve growth factor (NGF) binding the second extracellular immunoglobulin (TrkAIg2) domain triggers intracellular signaling cascades. In the periphery, this promotes the pain phenotype and, in the brain, cell survival or differentiation. Reproducible structural information and detailed validation of protein-ligand interactions aid drug discovery. However, the isolated TrkAIg2 domain crystallizes as a beta-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 (1)H-(15)N correlation spectra confirm that both NGF and a competing small molecule interact at the known binding interface in solution.
PDB ID: 4CRPDownload
MMDB ID: 125961
PDB Deposition Date: 2014/2/28
Updated in MMDB: 2018/05
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 4CRP: monomeric; determined by author and by software (PQS)
Molecular Components in 4CRP
Label Count Molecule
Protein (1 molecule)
1
High Affinity Nerve Growth Factor Receptor(Gene symbol: NTRK1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

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