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

Protein-protein Interfaces02:04

Protein-protein Interfaces

12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
Induced-fit Model01:13

Induced-fit Model

80.6K
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...
80.6K
Enzymes02:34

Enzymes

81.2K
Inside living organisms, enzymes act as catalysts for many biochemical reactions involved in cellular metabolism. The role of enzymes is to reduce the activation energies of biochemical reactions by forming complexes with its substrates. The lowering of activation energies favor an increase in the rates of biochemical reactions.
Enzyme deficiencies can often translate into life-threatening diseases. For example, a genetic abnormality resulting in the deficiency of the enzyme G6PD...
81.2K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

7.9K
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...
7.9K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.8K
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...
4.8K
Protein and Protein Structure02:15

Protein and Protein Structure

79.2K
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme...
79.2K

You might also read

Related Articles

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

Sort by
Same author

Unveiling the enzymatic activity of a dimeric LDH isoform and its implications for allosteric inhibition strategies.

Protein science : a publication of the Protein Society·2025
Same author

Structural and mechanistic insights into herpesvirus helicase-primase and its therapeutic inhibitors.

Nature microbiology·2025
Same author

Discovery of Potent Acyl-CoA Synthetase Long-Chain Family Member 4 (ACSL4) Inhibitors with Antiferroptotic Properties.

Journal of medicinal chemistry·2025
Same author

Structural insights into the interaction between testis-specific Y-encoded-like protein 5 and ubiquitin-specific protease 7.

Protein science : a publication of the Protein Society·2025
Same author

LIBX-A401: A Novel Selective Inhibitor of Acyl-CoA Synthetase Long Chain Family Member 4 (ACSL4) and Its Binding Mode.

Angewandte Chemie (International ed. in English)·2025
Same author

Examining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition.

Journal of medicinal chemistry·2025

Related Experiment Video

Updated: Jun 17, 2025

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
12:07

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET

Published on: October 9, 2021

3.4K

Structural Insights into Protein-Inhibitor Interactions in Human Tryptophan Dioxygenase.

Zachary Geeraerts1, Izumi Ishigami1, Ariel Lewis-Ballester1

  • 1Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, United States.

Journal of Medicinal Chemistry
|August 6, 2024
PubMed
Summary

Tryptophan dioxygenase (TDO) inhibitors are crucial for cancer immunotherapy. This study systematically evaluated TDO-inhibitor structures, offering insights for developing novel enzyme-selective inhibitors.

More Related Videos

Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition
08:31

Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition

Published on: October 3, 2018

8.5K
Benchtop Immobilized Metal Affinity Chromatography, Reconstitution and Assay of a Polyhistidine Tagged Metalloenzyme for the Undergraduate Laboratory
08:02

Benchtop Immobilized Metal Affinity Chromatography, Reconstitution and Assay of a Polyhistidine Tagged Metalloenzyme for the Undergraduate Laboratory

Published on: August 23, 2018

17.4K

Related Experiment Videos

Last Updated: Jun 17, 2025

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET
12:07

Chemical Modification of the Tryptophan Residue in a Recombinant Ca2+-ATPase N-domain for Studying Tryptophan-ANS FRET

Published on: October 9, 2021

3.4K
Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition
08:31

Anaerobic Protein Purification and Kinetic Analysis via Oxygen Electrode for Studying DesB Dioxygenase Activity and Inhibition

Published on: October 3, 2018

8.5K
Benchtop Immobilized Metal Affinity Chromatography, Reconstitution and Assay of a Polyhistidine Tagged Metalloenzyme for the Undergraduate Laboratory
08:02

Benchtop Immobilized Metal Affinity Chromatography, Reconstitution and Assay of a Polyhistidine Tagged Metalloenzyme for the Undergraduate Laboratory

Published on: August 23, 2018

17.4K

Area of Science:

  • Biochemistry
  • Structural Biology
  • Cancer Immunotherapy

Background:

  • Tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO) are key targets in cancer immunotherapy.
  • Numerous IDO inhibitors exist, with 52 TDO-inhibitor complex structures documented.
  • Development of TDO inhibitors has lagged, with only four TDO-inhibitor complex structures reported.

Purpose of the Study:

  • To systematically evaluate TDO structures complexed with competitive inhibitors.
  • To compare protein-inhibitor interactions for three distinct pharmacophores.
  • To provide insights for structure-based design of enzyme-selective TDO inhibitors.

Main Methods:

  • Systematic evaluation of TDO structures in complex with competitive inhibitors.
  • Comparative assessment of protein-inhibitor interactions.
  • Analysis of three pharmacophore types: imidazo-isoindole, indole-tetrazole, and indole-benzotriazole.

Main Results:

  • Detailed structural analysis of TDO in complex with three inhibitor pharmacophores.
  • Comparative insights into binding interactions and enzyme selectivity.
  • Identification of key structural features for TDO inhibition.

Conclusions:

  • Structural insights facilitate the design of selective TDO inhibitors.
  • Comparative analysis advances understanding of TDO-inhibitor interactions.
  • This work supports the development of novel cancer immunotherapies targeting TDO.