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Related Concept Videos

Thermodynamics: Chemical Potential and Activity01:10

Thermodynamics: Chemical Potential and Activity

1.1K
The effective concentration of a species in a solution can be expressed precisely in terms of its activity. Activity considers the effect of electrolytes present in the vicinity of the species of interest and depends on the ionic strength of the solution. The activity of a species is expressed as the product of molar concentration and the activity coefficient of the species.
The thermodynamic equilibrium constant is more accurately defined in terms of activity rather than concentration.
1.1K
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

5.9K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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ATP Driven Pumps I: An Overview01:27

ATP Driven Pumps I: An Overview

8.5K
ATP-driven pumps, also known as transport ATPases, are integral membrane proteins. They have binding sites for ATP located on the membrane's cytosolic side and the ion-conducting domain in the transmembrane region. These pumps use the free energy released from ATP hydrolysis to move the solutes across cell membranes against an electrochemical gradient.
There are four main types of ATP-driven pumps - P-type, V-type, F-type, and ABC transporter. All these pumps are of varying complexities and...
8.5K
Thermodynamics: Activity Coefficient01:24

Thermodynamics: Activity Coefficient

1.8K
Activity is the measure of the effective concentration of the species in solution. It can be expressed as the product of the molar concentration of the species and its activity coefficient. The activity coefficient is a dimensionless quantity and depends on the total ionic strength of the solution.
The activity coefficient is a measure of the deviation from ideal behavior. When the ionic strength of the solution is minimal, the activity coefficient of an ionic species is close to unity, making...
1.8K
Introduction to Mechanisms of Enzyme Catalysis01:13

Introduction to Mechanisms of Enzyme Catalysis

8.7K
For many years, scientists thought that enzyme-substrate binding took place in a simple "lock-and-key" fashion. This model stated that the enzyme and substrate fit together perfectly in one instantaneous step. However, current research supports a more refined view scientists call induced fit. The induced-fit model expands upon the lock-and-key model by describing a more dynamic interaction between enzyme and substrate. As the enzyme and substrate come together, their interaction causes...
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Effect of Temperature Change on Reaction Rate02:28

Effect of Temperature Change on Reaction Rate

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The Arrhenius equation,
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Related Experiment Video

Updated: Sep 8, 2025

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein
09:59

Functional Reconstitution and Channel Activity Measurements of Purified Wildtype and Mutant CFTR Protein

Published on: March 9, 2015

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Thermodynamic basis for CFTR activity potentiation.

Guangyu Wang

    Research Square
    |August 20, 2025
    PubMed
    Summary

    Trikafta modulators enhance cystic fibrosis transmembrane conductance regulator (hCFTR) function by stabilizing nucleotide-binding domain dimerization. Comparable thermostability between NBD1 and NBD2 is crucial for VX-770 potentiation, improving CFTR function.

    Keywords:
    allosteric couplingdigital biologyinterdomain interactionleast-stable interactionligand modulationmelting thresholdprotein stabilitythermodynamic signaturethermoring

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    A Fluorescence-Based Assay of Membrane Potential for High-Throughput Functional Study of Two Endogenous Ion Channels in Two Epithelial Cell Lines

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    Area of Science:

    • Biochemistry
    • Molecular Biology
    • Pharmacology

    Background:

    • Cystic fibrosis (CF) is caused by mutations in the human cystic fibrosis transmembrane conductance regulator (hCFTR) gene.
    • The most common CF mutation, F508del-hCFTR, exhibits defects in protein folding, stability, and gating.
    • Trikafta, a combination therapy, includes VX-770, VX-445, and VX-809, which partially restore hCFTR function.

    Purpose of the Study:

    • To elucidate the thermodynamic basis for VX-770's potentiation of Trikafta's activity.
    • To investigate the structural and interaction dynamics of NBD2 compared to NBD1 in response to ligand binding.
    • To understand the requirements for stabilizing the activated intermediate of hCFTR.

    Main Methods:

    • Thermostability assays were performed on NBD1 and NBD2.
    • Interdomain interactions were examined in the presence and absence of ligands.
    • Structural analysis focused on the impact of F508 mutation and ligand binding on NBDs.

    Main Results:

    • Comparable thermostability between dimerized NBD1 and NBD2 is essential for VX-770-mediated potentiation.
    • Ligand binding induces a global conformational change (induced fit) across interdomain interfaces.
    • This induced fit optimizes cooperative ligand-mediated NBD dimerization, enhancing channel activity.

    Conclusions:

    • Achieving balanced thermostability between NBD1 and NBD2 is critical for effective hCFTR potentiation by VX-770.
    • A global induced fit mechanism underlies the cooperative action of Trikafta components.
    • These findings provide insights for optimizing CFTR modulator therapies for cystic fibrosis treatment.