Related Experiment Video

Updated: Jan 28, 2026

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b
10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

9.0K

[Identifying Inhibitors of USP7-HDM2 Protein-Protein Interaction (PPI) by the in Silico Fragment-mapping Method]

Kensuke Misawa1, Shin-Ichiro Ozawa1, Tomoki Yoshida1

  • 1Department of Pharmaceutical Sciences, School of Pharmacy, Kitasato University.

Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan
|March 8, 2019
PubMed

Insights

Researchers identified new ways to inhibit cancer cell pathways by targeting USP7-HDM2 protein interactions. These novel inhibitors offer potential therapeutic strategies without affecting USP7 enzyme activity.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • The ubiquitin-proteome system regulates proteolysis, crucial in cancer development.
  • Ubiquitin-specific protease 7 (USP7) is a key regulator of the p53-human double minute 2 (HDM2) pathway in cancer cells.
  • Existing USP7 enzyme inhibitors face challenges with activity and selectivity for therapeutic use.

Purpose of the Study:

  • To discover novel inhibitors targeting the USP7-HDM2 protein-protein interaction (PPI).
  • To develop inhibitors that specifically block USP7-HDM2 PPI without impacting USP7 enzyme activity.

Main Methods:

  • Utilized the Fsubsite program and canonical subsite-fragment database (CSFDB) for fragment mapping on USP7.
  • Constructed 3D-pharmacophore models based on fragment arrangement patterns.
  • Performed 3D pharmacophore-based virtual screening of a commercial compound database.

Main Results:

  • Successfully mapped fragments onto the USP7 protein.
  • Developed 3D-pharmacophore models for USP7.
  • Identified promising USP7-HDM2 PPI inhibitor candidates through virtual screening.

Conclusions:

  • Novel USP7-HDM2 PPI inhibitors were identified.
  • The developed pharmacophore models and screening approach are effective for discovering PPI inhibitors.
  • These candidates hold potential for cancer therapy by targeting the USP7-HDM2 pathway.
Keywords:
dockingfragment mappingpharmacophoreprotein-protein interactionubiquitin-specific protease 7virtual screening

More Related Videos

Identifying Protein-protein Interaction Sites Using Peptide Arrays07:44

Identifying Protein-protein Interaction Sites Using Peptide Arrays

Published on: November 18, 2014

18.5K
Mapping Dysfunctional Protein-Protein Interactions in Disease09:39

Mapping Dysfunctional Protein-Protein Interactions in Disease

Published on: October 24, 2025

765

Related Concept Videos

Microtubule Associated Proteins (MAPs)01:42

Microtubule Associated Proteins (MAPs)

Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
5.9K
Protein Networks02:26

Protein Networks

An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.5K
Protein-protein Interfaces02:04

Protein-protein Interfaces

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...
14.7K
Protein and Protein Structure02:15

Protein and Protein Structure

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...
87.4K
What are Proteins?01:55

What are Proteins?

Overview
238.5K
G-protein Coupled Receptors01:21

G-protein Coupled Receptors

G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.
131.9K