One Type of Mutation Changes the Shape of the Binding Pocket

A mutation in the DNA that encodes the BCR-ABL protein changes the identity of a single amino acid: the conversion of threonine in the figure to the larger isoleucine.

This change constricts the shape of the ATP-binding pocket so that ATP can still bind but Gleevec no longer fits.

Cross section detail view of the wild-type binding pocket with threonine shows the irregular oblong purple shape labeled Gleevec fits in the pocket.
Wild-type with threonine
Cross section detail view of the mutant binding pocket with isoleucine shows the irregular oblong purple shape labeled Gleevec no longer fits in the pocket.
Mutant with isoleucine