Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.9K
Allosteric proteins have more than one ligand binding site; the binding of a ligand to any of these sites influences the binding of ligands to the other sites. When a protein is allosteric, its binding sites are called coupled or linked.  In the case of enzymes, the site that binds to the substrate is known as the active site and the other site is known as the regulatory site. When a ligand binds to the regulatory site, this leads to conformational changes in the protein that can influence...
4.9K
Conserved Binding Sites01:49

Conserved Binding Sites

4.3K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
4.3K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.0K
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...
8.0K
Introduction to Mechanisms of Enzyme Catalysis01:13

Introduction to Mechanisms of Enzyme Catalysis

8.6K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
8.6K
Induced-fit Model01:13

Induced-fit Model

81.9K
Most chemical reactions in cells require enzymes—biological catalysts that speed up the reaction without being consumed or permanently changed. They reduce the activation energy needed to convert the reactants into products. Enzymes are proteins, that usually work by binding to a substrate—a reactant molecule that they act upon.
Enzymes exhibit substrate specificity, meaning that they can only bind to certain substrates. This is mainly determined by the shape and chemical...
81.9K
Ligand Binding Sites02:40

Ligand Binding Sites

13.1K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
13.1K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Formate Dehydrogenase: The Role of the AMP Cofactor Fragment in Stabilization of the Transition State for Enzyme-Catalyzed Hydride Transfer.

ACS omega·2026
Same author

Enzyme Architecture: Activation of Phosphite Dehydrogenase-Catalyzed Hydride Transfer by NAD<sup>+</sup> Cofactor Fragments.

Biochemistry·2025
Same author

The Role of Protein Side Chains in Enzyme-Activating Conformational Changes: Lessons from Studies on Variant Enzymes.

Chemical reviews·2025
Same author

Bill Jencks' Model for Lifetime Enforced Changes in Reaction Mechanism: A Legacy for Physical Organic Chemistry.

Chemphyschem : a European journal of chemical physics and physical chemistry·2025
Same author

Glycerol 3-Phosphate Dehydrogenase Catalyzed Hydride Transfer: Enzyme Activation by Cofactor Pieces.

Biochemistry·2024
Same author

Glycerol 3-Phosphate Dehydrogenase: Role of the Protein Conformational Change in Activation of a Readily Reversible Enzyme-Catalyzed Hydride Transfer Reaction.

Biochemistry·2024

Related Experiment Video

Updated: Sep 4, 2025

Modeling an Enzyme Active Site using Molecular Visualization Freeware
14:37

Modeling an Enzyme Active Site using Molecular Visualization Freeware

Published on: December 25, 2021

10.1K

Enabling Role of Ligand-Driven Conformational Changes in Enzyme Evolution.

John P Richard1

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

Biochemistry
|July 13, 2022
PubMed
Summary

Enzymes use substrate binding energy to change shape, creating protein cages that stabilize transition states. This mechanism, seen in key metabolic enzymes, drives evolution of flexible protein structures like the TIM barrel.

More Related Videos

A New Screening Method for the Directed Evolution of Thermostable Bacteriolytic Enzymes
13:30

A New Screening Method for the Directed Evolution of Thermostable Bacteriolytic Enzymes

Published on: November 7, 2012

18.2K
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

14.4K

Related Experiment Videos

Last Updated: Sep 4, 2025

Modeling an Enzyme Active Site using Molecular Visualization Freeware
14:37

Modeling an Enzyme Active Site using Molecular Visualization Freeware

Published on: December 25, 2021

10.1K
A New Screening Method for the Directed Evolution of Thermostable Bacteriolytic Enzymes
13:30

A New Screening Method for the Directed Evolution of Thermostable Bacteriolytic Enzymes

Published on: November 7, 2012

18.2K
Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry
07:33

Analyzing Protein Architectures and Protein-Ligand Complexes by Integrative Structural Mass Spectrometry

Published on: October 15, 2018

14.4K

Area of Science:

  • Biochemistry and Molecular Biology
  • Enzyme Catalysis and Evolution

Background:

  • Many enzymes bind transition states more tightly than substrates.
  • Substrate binding energy is often used to induce protein conformational changes, forming stabilized complexes.
  • This strategy avoids irreversible binding of substrates.

Purpose of the Study:

  • To explore the role of substrate-induced conformational changes in enzyme catalysis and evolution.
  • To understand how enzymes evolve to stabilize transition states effectively.
  • To investigate the evolutionary advantage of flexible protein folds in enzyme development.

Main Methods:

  • The study proposes an evolutionary model based on analyzing known enzyme mechanisms.
  • It discusses the selection of variants that destabilize alternative protein conformers.
  • It examines the role of protein cages in stabilizing enzymatic transition states.

Main Results:

  • Enzymes utilize substrate binding energy to drive conformational changes, forming protein cages that stabilize transition states.
  • This mechanism is crucial for enzymes involved in major metabolic pathways like glycolysis and nucleotide biosynthesis.
  • The evolution of ligand-driven conformational changes favors flexible protein folds, such as the TIM barrel.

Conclusions:

  • Enzyme evolution favors conformational changes that stabilize transition states without irreversibly binding substrates.
  • The development of protein cages through conformational changes is a key evolutionary innovation.
  • Flexible protein folds like the TIM barrel emerged as a result of these evolutionary pressures, facilitating enzyme diversification.