Structural basis of kit activation by oncogenic mutations in the extracellular region reveals a zipper-like mechanism for ligand- dependent or oncogenic receptor tyrosine kinase activation

Structure

x-ray diffraction · 3 distinct chains · 2% helix, 58% strand (DSSP).

Ligands and binding sites

• NAG · 2-acetamido-2-deoxy-beta-D-glucopyranose · sugar · 3 copies · chains C, A, B
• CO · Cobalt (II) ion · metal · 5 copies · chains C, A

Binding sites are the residues within 4.5 Å of a ligand's heavy atoms.

Pockets

2 pockets found on a 1 Å grid, 1 with a druggability of 0.5 or more.

Interfaces

2 interfaces between chains.

• A–B · 1062 Ų buried · 9 hydrogen bonds · protein-protein
• C–A · 78 Ų buried · 0 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 5 disulfide, 3 glycan (disulfide, N-glycosylation).

Compared structures

• 4PGZ · Structural basis of KIT activation by oncogenic mutations in the extracellular region… · the same entry in another collection · chain C against C, TM-score 1.00
• P10721 · AlphaFold monomer V2.0 prediction for MAST/STEM cell growth factor receptor kit (P10721) · a predicted model of the same protein · chain C against A, TM-score 0.89

Analyse

• Open in the research workbench: secondary structure, accessibility, pockets, interfaces, conservation, variants, modifications, peptides and crosslinks on the 3D structure
• Every structure of UniProt P10721
• Elsewhere: RCSB PDB 4PGZ · PDBe 4PGZ · UniProt P10721