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

Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

7.8K
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...
7.8K
Allosteric Regulation01:08

Allosteric Regulation

57.3K
Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
57.3K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

4.7K
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...
4.7K
Network Function of a Circuit01:25

Network Function of a Circuit

242
Frequency response analysis in electrical circuits provides vital insights into a circuit's behavior as the frequency of the input signal changes. The transfer function, a mathematical tool, is instrumental in understanding this behavior. It defines the relationship between phasor output and input and comes in four types: voltage gain, current gain, transfer impedance, and transfer admittance. The critical components of the transfer function are the poles and zeros.
242
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

5.6K
Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
5.6K
MOSFET: Enhancement Mode01:22

MOSFET: Enhancement Mode

251
Enhancement-mode MOSFETs are pivotal components in electronics, distinguished by their capacity to act as highly efficient switches. They are part of the larger family of metal-oxide Semiconductor Field-Effect Transistors (MOSFETs). They are available in two types: p-channel and n-channel, each tailored to specific polarity operations.
In their basic form, enhancement-mode MOSFETs are typically non-conductive when the gate-source voltage (Vgs) is zero. This default 'off' state means no...
251

You might also read

Related Articles

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

Sort by
Same author

Inositol Thiophosphates as Inhibitors of Mammalian, Plant, and Fungal Phytases.

ACS chemical biology·2026
Same author

Synthesis and characterization of cortinarins - cryptic cyclic peptides from mushrooms of the genus <i>Cortinarius</i>.

Chemical science·2026
Same author

Polyfluoroalkyl-Tagged Cell-Penetrating Peptide-Additives Enhance Intracellular Protein Delivery via Sustained Monomeric Lipid Interaction.

Angewandte Chemie (International ed. in English)·2026
Same author

A Cryptic Pocket Allosterically Modulates Oligosaccharide Binding to DC-SIGN.

JACS Au·2026
Same author

The gut microbiome as a target in cancer immunotherapy: opportunities and challenges for drug development.

Nature reviews. Drug discovery·2025
Same author

Thiophosphate bioisosteres of inositol hexakisphosphate enhance binding affinity and residence time on bacterial virulence factors.

RSC chemical biology·2025

Related Experiment Video

Updated: May 17, 2025

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

453

Allosterically switchable network orients β-flap in Clostridioides difficile toxins.

Lauren M Finn1, Rebecca Cummer2, Bastien Castagner2

  • 1Department of Biology, Chemistry, and Pharmacy, Freie Universität Berlin, Berlin 14195, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|April 2, 2025
PubMed
Summary

Clostridioides difficile toxins use myo-inositol hexakisphosphate for self-cleavage. Molecular simulations reveal a switchable interaction network, not gradual shifts, drives this allosteric process, aiding drug development.

Keywords:
Clostridioides difficileTcdBallosteryfree energy surfacemolecular simulations

More Related Videos

Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes
10:10

Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes

Published on: October 4, 2018

8.8K
Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording
06:36

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording

Published on: September 1, 2022

3.6K

Related Experiment Videos

Last Updated: May 17, 2025

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
08:00

Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation

Published on: October 4, 2024

453
Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes
10:10

Analyzing the Size, Shape, and Directionality of Networks of Coupled Astrocytes

Published on: October 4, 2018

8.8K
Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording
06:36

Optrode Array for Simultaneous Optogenetic Modulation and Electrical Neural Recording

Published on: September 1, 2022

3.6K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Structural Biology

Background:

  • Allosteric proteins respond to ligand binding distant from the active site.
  • Clostridioides difficile toxins utilize myo-inositol hexakisphosphate for autoproteolysis within host cells.
  • Ligand binding induces conformational changes, notably in the beta-flap region, leading to two distinct orientations.

Purpose of the Study:

  • To elucidate the mechanism of allosteric transition in Clostridioides difficile toxins.
  • To identify key interactions driving the conformational shift upon cofactor binding.
  • To explore the potential for therapeutic targeting of toxin autoproteolysis.

Main Methods:

  • Extensive atomistic molecular dynamics simulations.
  • Computational and experimental mutagenesis.
  • Analysis of switchable interaction networks.

Main Results:

  • A mechanism for allosteric transition involving a switchable interaction network was uncovered.
  • The K600-E743 interaction pair is identified as the most significant contributor, accounting for ~70% of the allosteric effect.
  • The interaction network adopts two mutually exclusive configurations, rather than a gradual transition, for active and inactive states.

Conclusions:

  • The allosteric mechanism in C. difficile toxins relies on a discrete switchable interaction network.
  • This mechanism, characterized by distinct configurations, offers a new perspective on allostery.
  • Understanding this process can inform the development of drugs targeting C. difficile toxin autoproteolysis.