1) La descarga del recurso depende de la página de origen
2) Para poder descargar el recurso, es necesario ser usuario registrado en Universia


Opción 1: Descargar recurso

Opción 2: Descargar recurso

Detalles del recurso

Descripción

A series of tethered quaternary ammonium derivatives of Tyr have been incorporated into the binding site of the nicotinic acetylcholine receptor (nAChR) using the in vivo nonsense suppression method, producing constitutively active (self-gating) receptors. We have incorporated primary, secondary, and tertiary amine tethered agonists to give receptors whose constitutive activity can be modulated by pH. Lowering the pH protonates the tethered amine, giving it a positive charge and allowing it to reversibly activate the receptor. Tertiary and secondary tethered amines, TyrO3T and TyrO3S, have been successfully incorporated at α149 in the nAChR. Constitutive currents at pH 5.5 are 6 times those at pH 9.0. The pK_a of TyrO3T in the binding site appears to be 6 or lower, differing substantially from its pK_a in solution (∼9.3). This local pK_a perturbation has substantial implications for pharmacological research on the nAChR:  of the tertiary agonists considered, noracetylcholine experiences this pK_a perturbation, while nicotine does not.

Pertenece a

Caltech Authors  

Autor(es)

Petersson, E. James -  Choi, Anita -  Dahan, David S. -  Lester, Henry A. -  Dougherty, Dennis A. - 

Id.: 69790716

Versión: 1.0

Estado: Final

Tipo:  application/pdf -  application/pdf - 

Tipo de recurso: Article  -  PeerReviewed  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Formatos:  application/pdf -  application/pdf - 

Requerimientos técnicos:  Browser: Any - 

Relación: [References] http://resolver.caltech.edu/CaltechAUTHORS:20170414-144546207
[References] http://authors.library.caltech.edu/76579/

Fecha de contribución: 15-abr-2017

Contacto:

Localización:
* Petersson, E. James and Choi, Anita and Dahan, David S. and Lester, Henry A. and Dougherty, Dennis A. (2002) A Perturbed pK_a at the Binding Site of the Nicotinic Acetylcholine Receptor: Implications for Nicotine Binding. Journal of the American Chemical Society, 124 (43). pp. 12662-12663. ISSN 0002-7863. http://resolver.caltech.edu/CaltechAUTHORS:20170414-144546207

Otros recursos del mismo autor(es)

  1. A Computational Study of Cation−π Interactions vs Salt Bridges in Aqueous Media: Implications for Protein Engineering A direct comparison of the energetic significance of a representative salt bridge vs a representativ...
  2. Different Binding Orientations for the Same Agonist at Homologous Receptors: A Lock and Key or a Simple Wedge? Using unnatural amino acid mutagenesis, the binding site for serotonin at the novel Caenorhabditis e...
  3. A Computational Study of Nicotine Conformations in the Gas Phase and in Water The conformational preferences of nicotine in three protonation states and in the gas phase as well ...
  4. Using Physical Chemistry To Differentiate Nicotinic from Cholinergic Agonists at the Nicotinic Acetylcholine Receptor The binding of three distinct agonists - acetylcholine (ACh), nicotine, and epibatidine - to the nic...
  5. Caged Phosphoproteins We present the chemical and biological synthesis of caged phosphoproteins using the in vitro nonsens...

Otros recursos de la mismacolección

  1. Equivalence of Sobolev inequalities and Lieb-Thirring inequalities We show that, under very general definitions of a kinetic energy operator T, the Lieb–Thirring inequ...
  2. Measuring Flux Distributions for Diffusion in the Small-Numbers Limit For the classical diffusion of independent particles, Fick's law gives a well-known relationship bet...
  3. Mechanistic Investigation of β-Galactosidase-Activated MR Contrast Agents We report a mechanistic investigation of an isomeric series of β-galactosidase-activated magnetic re...
  4. Elastic-plastic bending of the lithosphere incorporating rock deformation data, with application to the structure of the Hawaiian archipelago An elastic-plastic lithosphere bending model incorporating rock deformation data has been developed ...
  5. Outstanding hydrogen evolution reaction catalyzed by porous nickel diselenide electrocatalysts To relieve our strong reliance on fossil fuels and to reduce greenhouse effects, there is an ever-gr...

Aviso de cookies: Usamos cookies propias y de terceros para mejorar nuestros servicios, para análisis estadístico y para mostrarle publicidad. Si continua navegando consideramos que acepta su uso en los términos establecidos en la Política de cookies.