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Related Concept Videos

Transition State Theory01:25

Transition State Theory

Transition-state theory, also known as activated-complex theory, provides a molecular-level explanation of reaction rates in both gas-phase and solution-phase reactions. It extends earlier kinetic models by considering the formation of a short-lived, high-energy configuration during a reaction.The progress of a chemical reaction can be represented using a reaction profile, which plots potential energy against the reaction coordinate. As two reactant molecules approach one another, their...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

Cooperative allosteric transitions can occur in multimeric proteins, where each subunit of the protein has its own ligand-binding site. When a ligand binds to any of these subunits, it triggers a conformational change that affects the binding sites in the other subunits; this can change the affinity of the other sites for their respective ligands. The ability of the protein to change the shape of its binding site is attributed to the presence of a mix of flexible and stable segments in the...
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

The equilibrium binding constant (Kb) quantifies the strength of a protein-ligand interaction. Kb can be calculated as follows when the reaction is at equilibrium:

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Related Experiment Video

Updated: May 15, 2026

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
05:51

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

Specificity in transition state binding: the Pauling model revisited.

Tina L Amyes1, John P Richard

  • 1Department of Chemistry, University at Buffalo , State University of New York, Buffalo, New York 14260-3000, United States.

Biochemistry
|January 19, 2013
PubMed
Summary

Enzymes accelerate reactions by specifically binding transition states, a concept supported by stable transition state analogs acting as inhibitors. This review explores how enzymes utilize binding energy, particularly with non-reacting substrate portions, to stabilize transition states and enhance catalysis.

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Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
06:48

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Published on: January 5, 2024

Related Experiment Videos

Last Updated: May 15, 2026

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method
05:51

Isotopic Effect in Double Proton Transfer Process of Porphycene Investigated by Enhanced QM/MM Method

Published on: July 19, 2019

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates
06:48

Single-Molecule Measurement of Protein Interaction Dynamics Within Biomolecular Condensates

Published on: January 5, 2024

Area of Science:

  • Biochemistry and enzymology
  • Chemical kinetics
  • Protein-ligand interactions

Background:

  • Linus Pauling's hypothesis posits that enzymes achieve high catalytic rates through specific binding of reaction transition states.
  • Stable transition-state analogs often function as potent enzyme inhibitors, providing early experimental validation for Pauling's proposal.
  • Understanding enzyme catalysis mechanisms is crucial for drug development and biotechnology.

Purpose of the Study:

  • To review experimental evidence supporting Pauling's transition state binding hypothesis for enzyme catalysis.
  • To explore how enzymes utilize binding energy from non-reacting substrate portions to stabilize transition states.
  • To examine specific examples of enzyme-substrate interactions and their contribution to rate acceleration.

Main Methods:

  • Review of existing experimental data and literature on enzyme kinetics and transition state binding.
  • Analysis of studies characterizing transition state binding specificity in various enzymatic reactions.
  • Examination of experimental evidence for enzyme conformational changes upon substrate binding.

Main Results:

  • Pauling's model adequately explains rate accelerations in many heterolytic enzymatic reactions involving high-energy intermediates.
  • Specific examples like ketosteroid isomerase, succinyl-coenzyme A:3-oxoacid CoA transferase (SCOT), and triosephosphate isomerase demonstrate significant transition state stabilization through specific binding interactions.
  • Enzymes like SCOT achieve rate enhancements of up to 10^12-fold by interacting with non-reacting parts of coenzyme A (CoA).
  • Interactions with substrate portions, such as the phosphodianion group, stabilize transition states by ~12 kcal/mol and can drive enzyme conformational changes.
  • Variable capping domains in enolase and dehalogenase superfamilies interact with non-reacting substrate parts, sequestering them from bulk solvent and activating the enzyme.

Conclusions:

  • Enzyme specificity for transition state binding is a key determinant of catalytic rate acceleration.
  • Binding interactions with non-reacting substrate portions play a critical role in stabilizing transition states and activating enzymes.
  • The reviewed evidence strongly supports Pauling's hypothesis and highlights the diverse strategies enzymes employ to achieve remarkable catalytic efficiency.