Video Experimental Relacionado
Updated: May 18, 2026
09:32
Light-mediated Reversible Modulation of the Mitogen-activated Protein Kinase Pathway during Cell Differentiation and Xenopus Embryonic Development
Published on: June 15, 2017
La modulación de un equilibrio conformacional preexistente sintoniza la actividad de la adenilato quinasa
Jörgen Ådén1, Abhinav Verma, Alexander Schug
1Department of Chemistry, Chemical Biological Center, Umeå University, SE-901 87 Umeå, Sweden.
Journal of the American Chemical Society
|September 12, 2012
Resumen
La plasticidad estructural en la adenilato quinasa (AK ((eco)) es clave para su actividad enzimática. La modulación de su equilibrio conformacional afecta tanto a la tasa de rotación como a la unión del sustrato, ofreciendo flexibilidad evolutiva.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Estructural Biología estructural.
- Enzimología Enzimología.
Sus antecedentes:
- La catálisis enzimática se basa en la plasticidad estructural para los ciclos de reacción.
- La adenilatocinasa de Escherichia coli (AK(eco)) existe en estados abierto (inactivo) y cerrado (activo).
- El volumen de negocios enzimático en AK ((eco) está vinculado a la vida útil de su conformación activa.
Objetivo del estudio:
- Para investigar el equilibrio conformacional de AK ((eco) en ausencia de sustrato.
- Para entender cómo este equilibrio influye en la catálisis enzimática.
- Explorar los efectos de las mutaciones y los osmolitos en la conformación y actividad de la AK (eco).
Principales métodos:
- Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN) Espectroscopía de Resonancia Magnética Nuclear (RMN).
- Simulaciones de dinámica molecular (DM). simulaciones de dinámica molecular (DM).
- Mutagénesis dirigida al sitio y tratamientos con osmolitos.
Principales resultados:
- La eliminación de un enlace de hidrógeno cambió el equilibrio a la conformación abierta, aumentando k(cat).
- La adición de TMAO cambió el equilibrio a la conformación cerrada, disminuyendo k(cat).
- Las constantes de Michaelis (K(M)) se correlacionan con los cambios de k(cat), lo que indica una afinidad de unión al sustrato alterada.
Conclusiones:
- El equilibrio conformacional preexistente impacta directamente en la catálisis enzimática.
- k ((cat) y K ((M) son interdependientes e influenciados por las poblaciones conformacionales.
- AK ((eco) exhibe flexibilidad para adaptar su constante de especificidad basada en presiones selectivas celulares.
Videos de Conceptos Relacionados
01:08Allosteric 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...
01:08Allosteric 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...
01:16Calmodulin-dependent Signaling
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:19Regulation of Metabolism
Cellular needs and conditions vary from cell to cell and change within individual cells over time. For example, the required enzymes and energetic demands of stomach cells are different from those of fat storage cells, skin cells, blood cells, and nerve cells. Furthermore, a digestive cell works much harder to process and break down nutrients during the time that closely follows a meal compared with many hours after a meal. As these cellular demands and conditions vary, so do the amounts and...
01:09GPCRs Regulate Adenylyl Cylase Activity
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 cells.
Two...
Two...
02:54Protein Kinases and Phosphatases
Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...