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Related Concept Videos

Ligand Binding and Linkage00:49

Ligand Binding and Linkage

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 the...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

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...
Cooperative Allosteric Transitions01:58

Cooperative Allosteric Transitions

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...
Allosteric Proteins-ATCase01:19

Allosteric Proteins-ATCase

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 pathway,...
Allosteric Regulation01:08

Allosteric Regulation

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...
Allosteric Regulation01:08

Allosteric Regulation

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...

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Related Experiment Video

Updated: Jun 8, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Docking to large allosteric binding sites on protein surfaces.

Ursula D Ramirez1, Faina Myachina, Linda Stith

  • 1Fox Chase Cancer Center, Philadelphia, PA 19111, USA.

Advances in Experimental Medicine and Biology
|September 25, 2010
PubMed
Summary

Researchers identified novel allosteric inhibitors for porphobilinogen synthase (PBGS) by targeting its inactive hexamer form. This approach stabilizes the hexamer, offering a new strategy for drug discovery targeting morpheeins.

Related Experiment Videos

Last Updated: Jun 8, 2026

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis
08:49

Incorporating Target Protein Structure Flexibility and Dynamics in Computational Drug Discovery Using Ensemble-Based Docking Analysis

Published on: June 20, 2025

Area of Science:

  • Biochemistry
  • Structural Biology
  • Drug Discovery

Background:

  • Porphobilinogen synthase (PBGS) exists in dynamic equilibrium between active octamer and inactive hexamer forms (morpheins).
  • The inactive hexamer possesses a unique surface cavity, absent in the active octamer, which is a potential target for allosteric inhibition.

Purpose of the Study:

  • To identify small molecules that stabilize the inactive hexamer of PBGS, acting as allosteric inhibitors.
  • To explore computational docking as a method for finding allosteric modulators of morpheeins.

Main Methods:

  • Utilized GLIDE software for virtual screening of a 250,000-molecule library.
  • Focused docking on the hexamer-specific surface cavity of PBGS from Yersinia enterocolitica.
  • Performed in vitro testing of 86 selected compounds for hexamer stabilization.

Main Results:

  • Identified five compounds that demonstrated hexamer stabilization in vitro.
  • The computational approach successfully enriched the library for potential allosteric inhibitors.
  • Confirmed the feasibility of targeting morpheein quaternary structure dynamics.

Conclusions:

  • Computational docking to surface cavities is an effective strategy for discovering allosteric modulators.
  • The identified compounds represent potential leads for developing novel PBGS inhibitors.
  • This study highlights the therapeutic potential of targeting protein quaternary structure dynamics.