scholarly journals Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor

2021 ◽  
pp. 184-196
Author(s):  
Matthew T. Eddy ◽  
Ming-Yue Lee ◽  
Zhan-Guo Gao ◽  
Kate L. White ◽  
Tatiana Didenko ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Intracellular Signaling ◽  
Drug Binding ◽  
A2a Adenosine Receptor ◽  
Allosteric Coupling

scholarly journals Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor

Cell ◽  
2018 ◽  
Vol 172 (1-2) ◽  
pp. 68-80.e12 ◽  
Author(s):  
Matthew T. Eddy ◽  
Ming-Yue Lee ◽  
Zhan-Guo Gao ◽  
Kate L. White ◽  
Tatiana Didenko ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Intracellular Signaling ◽  
Drug Binding ◽  
A2a Adenosine Receptor ◽  
Allosteric Coupling

scholarly journals Allosteric Coupling of Drug Binding and Intracellular Signaling in the A2A Adenosine Receptor

2018 ◽  
Author(s):  
Matthew T. Eddy ◽  
Ming-Yue Lee ◽  
Zhanguo Gao ◽  
Tatiana Didenko ◽  
Reto Horst ◽  
...  
Keyword(s):  
Adenosine Receptor ◽  
Intracellular Signaling ◽  
Drug Binding ◽  
Allosteric Coupling

scholarly journals Extrinsic Tryptophans as NMR Probes of Allosteric Coupling in Membrane Proteins: Application to the A2A Adenosine Receptor

2018 ◽  
Vol 140 (26) ◽  
pp. 8228-8235 ◽  
Author(s):  
Matthew T. Eddy ◽  
Zhan-Guo Gao ◽  
Philip Mannes ◽  
Nilkanth Patel ◽  
Kenneth A. Jacobson ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Adenosine Receptor ◽  
A2a Adenosine Receptor ◽  
Allosteric Coupling

scholarly journals A2A adenosine receptor functional states characterized by 19F-NMR

2018 ◽  
Vol 115 (50) ◽  
pp. 12733-12738 ◽  
Author(s):  
Lukas Sušac ◽  
Matthew T. Eddy ◽  
Tatiana Didenko ◽  
Raymond C. Stevens ◽  
Kurt Wüthrich
Keyword(s):  
Adenosine Receptor ◽  
Drug Targets ◽  
High Sensitivity ◽  
Receptor Activation ◽  
Drug Binding ◽  
A2a Adenosine Receptor ◽  
Drug Binding Site ◽  
Nmr Study ◽  
The Difference ◽  
Intracellular Binding

The human proteome contains 826 G protein-coupled receptors (GPCR), which control a wide array of key physiological functions, making them important drug targets. GPCR functions are based on allosteric coupling from the extracellular orthosteric drug binding site across the cell membrane to intracellular binding sites for partners such as G proteins and arrestins. This signaling process is related to dynamic equilibria in conformational ensembles that can be observed by NMR in solution. A previous high-resolution NMR study of the A2A adenosine receptor (A2AAR) resulted in a qualitative characterization of a network of such local polymorphisms. Here, we used 19F-NMR experiments with probes at the A2AAR intracellular surface, which provides the high sensitivity needed for a refined description of different receptor activation states by ensembles of simultaneously populated conformers and the rates of exchange among them. We observed two agonist-stabilized substates that are not measurably populated in apo-A2AAR and one inactive substate that is not seen in complexes with agonists, suggesting that A2AAR activation includes both induced fit and conformational selection mechanisms. Comparison of A2AAR and a constitutively active mutant established relations between the 19F-NMR spectra and signaling activity, which enabled direct assessment of the difference in basal activity between the native protein and its variant.

Ligand-Based Virtual Screening Using Tailored Ensembles: A Prioritization Tool for Dual A2A Adenosine Receptor Antagonists / Monoamine Oxidase B Inhibitors

2016 ◽  
Vol 22 (21) ◽  
pp. 3082-3096 ◽  
Author(s):  
Aliuska Morales Helguera ◽  
Yunierkis Perez-Castillo ◽  
M. Natália D.S. Cordeiro ◽  
Eduardo Tejera ◽  
César Paz-y-Miño ◽  
...  
Keyword(s):  
Virtual Screening ◽  
Monoamine Oxidase ◽  
Adenosine Receptor ◽  
Monoamine Oxidase B ◽  
Receptor Antagonists ◽  
A2a Adenosine Receptor
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