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 Sites02:40

Ligand Binding Sites

15.7K
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...
15.7K
Ligand Binding Sites02:40

Ligand Binding Sites

9.1K
9.1K
Ligand Binding and Linkage00:49

Ligand Binding and Linkage

5.9K
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...
5.9K
Conserved Binding Sites01:49

Conserved Binding Sites

5.3K
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...
5.3K
The Equilibrium Binding Constant and Binding Strength02:18

The Equilibrium Binding Constant and Binding Strength

15.6K
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:
15.6K
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

9.4K
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...
9.4K

You might also read

Related Articles

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

Sort by
Same author

LCK-targeting molecular glues overcome resistance to inhibitor-based therapy in T-cell acute lymphoblastic leukemia.

Blood·2026
Same author

Harvest Process and Affinity Resin Selection Impacts on Adeno-Associated Virus Residual Host Cell Protein Retention.

Human gene therapy·2026
Same author

Crop-OCT: a Fully Integrated Imageomics Pipeline to Identify Regional and Focal Retinopathy in Murine Models.

bioRxiv : the preprint server for biology·2026
Same author

Targeting glycerophospholipid biosynthesis overcomes chemoresistance driven by SLFN11 loss in Ewing sarcoma.

Cell death & disease·2026
Same author

Modeling and Functional Characterization of Reconstituted Efflux Pump Components from Heterologous Gram-Negative Bacteria.

ACS infectious diseases·2026
Same author

Direct-to-Biology Enabled Molecular Glue Discovery.

Journal of the American Chemical Society·2025

Related Experiment Video

Updated: Mar 26, 2026

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

3.9K

Monitoring Ligand-Induced Protein Ordering in Drug Discovery.

Christy R Grace1, David Ban1, Jaeki Min2

  • 1Department of Structural Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.

Journal of Molecular Biology
|January 27, 2016
PubMed
Summary

Researchers developed small molecules to restore tumor suppressor p53 activity by inhibiting Mdm2 and MdmX. NMR structures reveal how these compounds bind MdmX, guiding future drug optimization for cancer therapy.

Keywords:
MdmXNutlindrug discoverynuclear magnetic resonancep53

More Related Videos

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
08:21

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

7.5K
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

15.1K

Related Experiment Videos

Last Updated: Mar 26, 2026

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA
10:21

Author Spotlight: Streamlining Protein Target Prediction and Validation via Molecular Docking and CETSA

Published on: February 23, 2024

3.9K
Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery
08:21

Monitoring GPCR-β-arrestin1/2 Interactions in Real Time Living Systems to Accelerate Drug Discovery

Published on: June 28, 2019

7.5K
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

15.1K

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Medicinal Chemistry

Background:

  • Many cancers retain wild-type p53 but have reduced activity due to Mdm2/MdmX overexpression.
  • Inhibiting Mdm2 or MdmX with small molecules can restore endogenous p53 tumor suppressor function.

Purpose of the Study:

  • To determine the solution structures of MdmX in complex with small molecule inhibitors.
  • To compare the binding of small molecules to MdmX with the binding of p53 peptide.
  • To establish structure-activity relationships for small molecules targeting MdmX.

Main Methods:

  • NMR spectroscopy to determine solution structures of MdmX-compound complexes.
  • Affinity measurements (Kd values) for MdmX:p53 peptide and MdmX:small molecule interactions.
  • Cell-based assays to assess p53 activation and p21(Cip1) expression.

Main Results:

  • NMR structures reveal MdmX:p53 peptide binding induces extensive hydrogen bonding and protein order.
  • Small molecules bind MdmX with weaker affinity and induce incomplete hydrogen bond networks.
  • Despite weaker binding, compounds activated p53 and induced p21(Cip1) in MdmX-overexpressing cells.

Conclusions:

  • Small molecules targeting MdmX/Mdm2 can restore p53 tumor suppressor activity.
  • NMR-guided analysis of protein order provides insights into structure-activity relationships.
  • Further optimization of MdmX inhibitors is feasible for cancer treatment.