Unknown

Dataset Information

0

Revisiting the Allosteric Regulation of Sodium Cation on the Binding of Adenosine at the Human A2A Adenosine Receptor: Insights from Supervised Molecular Dynamics (SuMD) Simulations.


ABSTRACT: One of the most intriguing findings highlighted from G protein-coupled receptor (GPCR) crystallography is the presence, in many members of class A, of a partially hydrated sodium ion in the middle of the seven transmembrane helices (7TM) bundle. In particular, the human adenosine A2A receptor (A2A AR) is the first GPCR in which a monovalent sodium ion was crystallized in a distal site from the canonical orthosteric one, corroborating, from a structural point of view, its role as a negative allosteric modulator. However, the molecular mechanism by which the sodium ion influences the recognition of the A2A AR agonists is not yet fully understood. In this study, the supervised molecular dynamics (SuMD) technique was exploited to analyse the sodium ion recognition mechanism and how its presence influences the binding of the endogenous agonist adenosine. Due to a higher degree of flexibility of the receptor extracellular (EC) vestibule, we propose the sodium-bound A2A AR as less efficient in stabilizing the adenosine during the different steps of binding.

SUBMITTER: Bissaro M 

PROVIDER: S-EPMC6695830 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Revisiting the Allosteric Regulation of Sodium Cation on the Binding of Adenosine at the Human A<sub>2A</sub> Adenosine Receptor: Insights from Supervised Molecular Dynamics (SuMD) Simulations.

Bissaro Maicol M   Bolcato Giovanni G   Deganutti Giuseppe G   Sturlese Mattia M   Moro Stefano S  

Molecules (Basel, Switzerland) 20190729 15


One of the most intriguing findings highlighted from G protein-coupled receptor (GPCR) crystallography is the presence, in many members of class A, of a partially hydrated sodium ion in the middle of the seven transmembrane helices (7TM) bundle. In particular, the human adenosine A<sub>2A</sub> receptor (A<sub>2A</sub> AR) is the first GPCR in which a monovalent sodium ion was crystallized in a distal site from the canonical orthosteric one, corroborating, from a structural point of view, its ro  ...[more]

Similar Datasets

| S-EPMC7188303 | biostudies-literature
| S-EPMC6445292 | biostudies-literature
| S-EPMC5741531 | biostudies-literature
| S-EPMC8730723 | biostudies-literature
| S-EPMC5893540 | biostudies-literature
| S-EPMC7278174 | biostudies-literature
| S-EPMC6067640 | biostudies-literature
| S-EPMC7057144 | biostudies-literature
| S-EPMC7290864 | biostudies-literature
| S-EPMC1449996 | biostudies-literature