Crystal structure of EGFR-T790M/V948R in complex with spebrutinib and EAI001

Structure

x-ray diffraction · 2 distinct chains · 42% helix, 19% strand (DSSP).

Ligands and binding sites

• 57N · (2R)-2-(1-oxo-1,3-dihydro-2H-isoindol-2-yl)-2-phenyl-N-(1,3-thiazol-2-yl)acetamide · ligand · 2 copies · chains A, B
• 7G9 · ~{N}-[3-[[5-fluoranyl-2-[[4-(2-methoxyethoxy) phenyl]amino]pyrimidin-4-yl]amino]phenyl]propanamide · ligand · 2 copies · chains A, B
• SO4 · Sulfate ion · ion · 4 copies · chains A, B
• CL · Chloride ion · ion · chains A

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

Pockets

6 pockets found on a 1 Å grid, 3 with a druggability of 0.5 or more.

Interfaces

1 interface between chains.

• A–B · 1285 Ų buried · 15 hydrogen bonds · protein-protein

Modifications

Observed in the structure: 2 covalent (covalent ligand).

Compared structures

• 7A2A · Crystal Structure of EGFR-T790M/V948R in Complex with Spebrutinib and EAI001 · the same entry in another collection · chain A against A, TM-score 1.00
• P00533 · AlphaFold monomer V2.0 prediction for epidermal growth factor receptor (P00533) · a predicted model of the same protein · chain A against A, TM-score 0.98

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 P00533
• Elsewhere: RCSB PDB 7A2A · PDBe 7A2A · UniProt P00533