Theory 37/Enzyme Kinetics
Promiscuity Is a Complementarity Ratio
The claim
Enzyme promiscuity is set by the ratio of transition-state complementarity to substrate fit, so a rigid active site is less promiscuous than a flexible one of the same affinity.
01The mechanism
Catalysis requires stabilising a transition state; a site that fits many substrates well enough to bind but only one well enough to stabilise is poorly promiscuous.
02Predictions
- P1Promiscuity should track the ratio.
- P2Affinity alone should mispredict.
03Refutation
Promiscuity tracking affinity would remove the complementarity term.