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

5.2K
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...
5.2K
GPCR Desensitization01:12

GPCR Desensitization

7.3K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
7.3K
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

6.2K
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...
6.2K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

8.4K
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...
8.4K
The Two-State Receptor Model01:29

The Two-State Receptor Model

2.8K
The two-state receptor model explains a drug's interaction with receptors, such as G protein-coupled receptors and ligand-gated ion channels, to induce or inhibit a biological response. When no natural ligands are present, a receptor exists in an equilibrium of inactive (Ri) and active (Ra) conformations. The inactive form does not produce a response, while the active form generates a basal effect known as constitutive activity.
The binding affinity of a drug determines its interaction with...
2.8K

You might also read

Related Articles

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

Sort by
Same author

Molecular Hybridization of Clinically Relevant P2X7 Antagonists.

ChemMedChem·2026
Same author

Bordetella pertussis: emerging epidemiology, diagnosis and management.

Pathology·2026
Same author

Psychedelics and Entactogens.

Journal of medicinal chemistry·2026
Same author

Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.

Nature communications·2026
Same author

Lactococcus garvieae prosthetic aortic and mitral valve endocarditis with multiple embolic complications: a case report.

Access microbiology·2026
Same author

Histone methyltransferase PRDM9 promotes survival of drug-tolerant persister cells in glioblastoma.

Nature communications·2025

Related Experiment Video

Updated: Nov 20, 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

3.6K

Reversing binding sensitivity to A147T translocator protein.

Sophie V Vo1, Samuel D Banister2,3, Isaac Freelander3

  • 1Faculty of Medicine and Health , The University of Sydney , Sydney , New South Wales 2006 , Australia.

RSC Medicinal Chemistry
|January 22, 2021
PubMed
Summary

Developing neuroinflammation imaging agents targeting the translocator protein (TSPO) is crucial. This study identified molecular strategies to improve binding affinity for the common A147T TSPO polymorphism, enhancing PET ligand development.

More Related Videos

Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis
08:09

Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis

Published on: January 7, 2017

11.0K
Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
04:47

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System

Published on: May 22, 2020

3.8K

Related Experiment Videos

Last Updated: Nov 20, 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

3.6K
Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis
08:09

Mapping the Binding Site of an Aptamer on ATP Using MicroScale Thermophoresis

Published on: January 7, 2017

11.0K
Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
04:47

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System

Published on: May 22, 2020

3.8K

Area of Science:

  • Neuroscience
  • Radiochemistry
  • Pharmacology

Background:

  • The translocator protein (TSPO) is a key target for neuroinflammation imaging agents.
  • Clinical use of TSPO PET ligands like [11C]DPA-713 is limited by the A147T polymorphism, which reduces ligand affinity.
  • Understanding binding differences between wild-type (WT) and A147T TSPO is essential for developing effective imaging agents.

Purpose of the Study:

  • To identify specific molecular features of DPA-713 and related compounds that influence binding to WT and A147T TSPO.
  • To guide the design of novel TSPO PET ligands with improved affinity for both TSPO variants.

Main Methods:

  • Synthesis and evaluation of DPA-713 derivatives with modifications to the heterocyclic core and hydrogen bonding groups.
  • Assessment of ligand binding affinity to WT and A147T TSPO variants.

Main Results:

  • Modifications to the nitrogen position and number in the heterocyclic core affected WT and A147T binding similarly.
  • Incorporating hydrogen bonding groups into an indole core significantly enhanced binding to A147T TSPO compared to WT.
  • This strategy yielded compounds with up to tenfold greater affinity for A147T TSPO.

Conclusions:

  • Hydrogen bonding interactions are critical for achieving high affinity binding to the A147T TSPO polymorphism.
  • These findings provide a rational basis for designing next-generation TSPO PET ligands capable of binding both A147T and WT variants for improved neuroinflammation imaging.