Video Experimental Relacionado
Updated: Apr 19, 2026
08:28
Single-molecule Manipulation of G-quadruplexes by Magnetic Tweezers
Published on: September 19, 2017
8.8K
Cambios conformacionales inducidos por ligandos con eyección de cationes al unirse al ADN telomérico humano
Adrien Marchand1, Anton Granzhan, Keisuke Iida
1IECB, ARNA Laboratory, University of Bordeaux , 33600 Pessac, France.
Journal of the American Chemical Society
|December 20, 2014
Resumen
Los ligandos potentes pueden alterar las estructuras del ADN telomérico humano G-cuadruplex. Este cambio conformacional a una forma antiparalela implica la eliminación de iones de potasio, un factor crítico en el diseño del ligando.
Área de la Ciencia:
- La bioquímica es la bioquímica.
- Biología Molecular Biología Molecular
- Química Medicinal La Química Medicinal es el campo de la Química Medicinal.
Sus antecedentes:
- El ADN telomérico humano G-cuadruplexos exhiben polimorfismo estructural bajo condiciones fisiológicas.
- La conmutación conformacional inducida por ligandos de los cuádruplexos G a menudo se descuida en el modelado computacional.
- Comprender estas dinámicas es crucial para desarrollar terapias dirigidas.
Objetivo del estudio:
- Para investigar el impacto de los potentes ligandos G-cuadruplex en la conformación del ADN telomérico G-cuadruplex.
- Para determinar si la unión de ligandos induce cambios estructurales específicos y la dinámica del catión asociada.
- Para comparar los efectos de diferentes ligandos en varias estructuras G-cuadruplex.
Principales métodos:
- Espectroscopia de dicroísmo circular para evaluar la conformación del ADN.
- Espectrometría de masas por electrospray para analizar la coordinación de iones de potasio.
- Estudios vinculantes con ligandos G-cuadruplex establecidos y de control.
Principales resultados:
- Los ligandos potentes (360A, Phen-DC3, piridostatina) indujeron un cambio a una estructura G-cuadruplex antiparalela.
- Este cambio de conformación fue acompañado por la eliminación de un ion de potasio.
- Los ligandos de control no indujeron la eliminación de cationes, y un ligando incluso aumentó la absorción de potasio.
Conclusiones:
- Los ligandos de alta afinidad pueden inducir una conmutación conformacional significativa en los telómeros humanos G-cuadruplexos.
- La eliminación de cationes mediada por ligandos es una característica clave de este cambio conformacional.
- Estos hallazgos son vitales para el diseño racional de fármacos dirigidos al G-cuadruplex.
Videos de Conceptos Relacionados
02:41Telomeres and Telomerase
28.9K
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded...
28.9K
00:49Ligand Binding and Linkage
6.0K
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...
6.0K
01:03Single-Strand DNA Binding Proteins
17.4K
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
17.4K
02:40Ligand Binding Sites
15.9K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.9K
01:22Activation and Inactivation of G Proteins
12.8K
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high...
12.8K
01:12GPCR Desensitization
8.9K
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
8.9K