AFN941 binding WT EGFR TKD(L) & G719S mutant(R)

sketchfab

EGFR is a receptor tyrosine kinase that plays a critical role in the signal transduction pathway underpinning cell proliferation & differentiation. Its tyrosine kinase domain (TKD) functions to bind and facilitate phosphate transfer from ATP & therefore plays a critical role in EGFR function. Inhibitors have been developed to target the ATP binding cleft of EGFR TKD, thereby preventing substrate phosphorylation & inhibiting signal transduction. Specific EGFR TKD mutations, such as G719S, are responsible for a subset of non-small cell lung cancers. This Sketchfab display compares the binding interaction of the non-specific EGFR inhibitor AFN941 with the human WT EGFR TKD & G719S EGFR TKD mutant. The mutation from glycine to serine causes a conformational change in the P-loop, resulting in inhibitor displacement & the formation of additional hydrogen bonds with residues Gln791 & Arg841. This comparison highlights that protein mutation can alter protein:drug binding interactions.