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Videos de Conceptos Relacionados

Thermodynamics: Chemical Potential and Activity01:10

Thermodynamics: Chemical Potential and Activity

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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.
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GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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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

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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...
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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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Video Experimental Relacionado

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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Base termodinámica para la potenciación de la actividad CFTR

Guangyu Wang

    Research square
    |August 20, 2025
    PubMed
    Resumen

    Los moduladores de Trikafta mejoran la función del regulador de conductividad transmembrana de la fibrosis quística (hCFTR) mediante la estabilización de la dimerización del dominio de unión de nucleótidos. La termostabilidad comparable entre NBD1 y NBD2 es crucial para la potenciación de VX-770, mejorando la función CFTR.

    Palabras clave:
    Acoplamiento alostéricoBiología digitalInteracción entre dominiosinteracción menos estableModulación del ligandoumbral de fusiónEstabilidad de las proteínasfirma termodinámicatérmico

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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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    Área de la Ciencia:

    • La bioquímica
    • Biología molecular
    • Farmacología

    Sus antecedentes:

    • La fibrosis quística (FC) es causada por mutaciones en el gen regulador de conductividad transmembrana de la fibrosis quística humana (hCFTR).
    • La mutación CF más común, F508del-hCFTR, exhibe defectos en el plegamiento, la estabilidad y el encierro de proteínas.
    • Trikafta, una terapia combinada, incluye VX-770, VX-445 y VX-809, que restauran parcialmente la función de hCFTR.

    Objetivo del estudio:

    • Para aclarar la base termodinámica de la potenciación de la actividad de Trikafta por VX-770.
    • Investigar la dinámica estructural y de interacción de NBD2 en comparación con NBD1 en respuesta a la unión del ligando.
    • Comprender los requisitos para la estabilización del intermedio activado de hCFTR.

    Principales métodos:

    • Se realizaron ensayos de termostabilidad en NBD1 y NBD2.
    • Se examinaron las interacciones interdominianas en presencia y ausencia de ligandos.
    • El análisis estructural se centró en el impacto de la mutación F508 y la unión del ligando en los NBD.

    Principales resultados:

    • La termostabilidad comparable entre el NBD1 dimerizado y el NBD2 es esencial para la potenciación mediada por VX-770.
    • La unión de ligandos induce un cambio conformacional global (ajuste inducido) a través de las interfaces de dominio.
    • Este ajuste inducido optimiza la dimerización NBD cooperativa mediada por ligando, mejorando la actividad del canal.

    Conclusiones:

    • El logro de una termostabilidad equilibrada entre NBD1 y NBD2 es fundamental para la potenciación efectiva de hCFTR por VX-770.
    • El mecanismo de ajuste inducido global subyace a la acción cooperativa de los componentes de Trikafta.
    • Estos hallazgos proporcionan información para optimizar las terapias de modulación de CFTR para el tratamiento de la fibrosis quística.