Early lock-and-key models pictured an enzyme as a rigid template matching a rigid substrate. Which observation most directly motivated the modern induced-fit model?

Core Concept

Structural studies revealed that many active sites fit their substrates closely only after binding begins. Induced fit describes a flexible active site that molds around the substrate, straining its bonds and positioning catalytic side chains for attack, which raises both specificity and rate. Gene rewriting during catalysis contradicts molecular biology, universal tighter product binding would jam enzymes with product, and flexibility after the cycle would not improve catalysis while substrate is bound.