ChemInform · 2005 · 19 citations · 1 references
Life SciencesBiochemistryChemistryBiocatalysisCatalysisEnzymologyCatalytic MechanismsEnzyme ActivationEnzyme CatalysisEnzyme FunctionEnzyme KineticsEnzyme SpecificityEnzyme Reaction MechanismsEnzyme ThermodynamicsEnzyme-substrate Binding KineticsEnzymesSubstrate Transition State ComplementarityThermodynamics Of Enzyme CatalysisTransition State Binding EnergyTransition State Theory In Enzymology
Pauling’s complementarity paradigm explains up to 11 orders of magnitude acceleration, yet most enzymes surpass this limit, indicating additional catalytic mechanisms. Highly proficient enzymes (>10¹¹ M⁻¹) achieve over 15 kcal mol⁻¹ transition‑state binding through covalent interactions that alter the reaction mechanism, demonstrating that enzymes participate directly in the reaction rather than merely complementing the transition state.
Pauling proposed that "enzymes are molecules that are complementary in structure to the activated complexes of the reactions that they catalyze, ..., [rather than] entering into reactions". This paradigm has dominated thinking in the field. While complementarity of the type proposed by Pauling can account for acceleration up to 11 orders of magnitude, most enzymes exceed that proficiency. Enzymes with proficiencies ((kcat/KM)/kuncat) > 1011 M-1 achieve over 15 kcal/mol of "transition state binding" not merely by a concatenation of noncovalent effects but by covalent bond formation between enzyme or cofactor and transition state, involving a change in mechanism from that in aqueous solution. Enzymes enter into reactions with substrates and do not merely complement the transition states of the uncatalyzed reactions.
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