scholarly journals G-Protein coupled receptors: structure and function in drug discovery

RSC Advances ◽  
2020 ◽  
Vol 10 (60) ◽  
pp. 36337-36348 ◽  
Author(s):  
Chiemela S. Odoemelam ◽  
Benita Percival ◽  
Helen Wallis ◽  
Ming-Wei Chang ◽  
Zeeshan Ahmad ◽  
...  
Keyword(s):  
Drug Discovery ◽  
G Protein ◽  
Mammalian Genome ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
And Function ◽  
G Protein Coupled

The G-protein coupled receptors (GPCRs) superfamily comprise similar proteins arranged into families or classes thus making it one of the largest in the mammalian genome.

scholarly journals G protein-coupled receptors: structure- and function-based drug discovery

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Dehua Yang ◽  
Qingtong Zhou ◽  
Viktorija Labroska ◽  
Shanshan Qin ◽  
Sanaz Darbalaei ◽  
...  
Keyword(s):  
Drug Discovery ◽  
G Protein ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
Comprehensive Overview ◽  
Ligand Screening ◽  
Important Field ◽  
Common Interests ◽  
And Function ◽  
G Protein Coupled

AbstractAs one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in the understanding of their structure–function relationships that facilitated drug development at an unprecedented pace. This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.

Structure and Function of G Protein-Coupled Receptors

1994 ◽  
Vol 63 (1) ◽  
pp. 101-132 ◽  
Author(s):  
C D Strader ◽  
T M Fong ◽  
M R Tota ◽  
D Underwood ◽  
R A F Dixon
Keyword(s):  
G Protein ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
And Function ◽  
G Protein Coupled

scholarly journals First Principles Predictions of the Structure and Function of G-Protein-Coupled Receptors: Validation for Bovine Rhodopsin

2004 ◽  
Vol 86 (4) ◽  
pp. 1904-1921 ◽  
Author(s):  
Rene J. Trabanino ◽  
Spencer E. Hall ◽  
Nagarajan Vaidehi ◽  
Wely B. Floriano ◽  
Victor W.T. Kam ◽  
...  
Keyword(s):  
G Protein ◽  
First Principles ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
Bovine Rhodopsin ◽  
And Function ◽  
G Protein Coupled

scholarly journals Prediction of structure and function of G protein-coupled receptors

2002 ◽  
Vol 99 (20) ◽  
pp. 12622-12627 ◽  
Author(s):  
N. Vaidehi ◽  
W. B. Floriano ◽  
R. Trabanino ◽  
S. E. Hall ◽  
P. Freddolino ◽  
...  
Keyword(s):  
G Protein ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
And Function ◽  
G Protein Coupled

scholarly journals Structural and Functional Characterization of G Protein-Coupled Receptors with Deep Mutational Scanning

2019 ◽  
Author(s):  
Eric M. Jones ◽  
Nathan B. Lubock ◽  
AJ Venkatakrishnan ◽  
Jeffrey Wang ◽  
Alex M. Tseng ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Functional Characterization ◽  
Structure And Function ◽  
G Protein Coupled Receptors ◽  
Single Amino Acid ◽  
Loss Of Function ◽  
And Function ◽  
Drug Receptors ◽  
G Protein Coupled

AbstractIn humans, the 813 G protein-coupled receptors (GPCRs) are responsible for transducing diverse chemical stimuli to alter cell state, and are the largest class of drug targets. Their myriad structural conformations and various modes of signaling make it challenging to understand their structure and function. Here we developed a platform to characterize large libraries of GPCR variants in human cell lines with a barcoded transcriptional reporter of G-protein signal transduction. We tested 7,800 of 7,828 possible single amino acid substitutions to the beta-2 adrenergic receptor (β2AR) at four concentrations of the agonist isoproterenol. We identified residues specifically important for β2AR signaling, mutations in the human population that are potentially loss of function, and residues that modulate basal activity. Using unsupervised learning, we resolve residues critical for signaling, including all major structural motifs and molecular interfaces. We also find a previously uncharacterized structural latch spanning the first two extracellular loops that is highly conserved across Class A GPCRs and is conformationally rigid in both the inactive and active states of the receptor. More broadly, by linking deep mutational scanning with engineered transcriptional reporters, we establish a generalizable method for exploring pharmacogenomics, structure and function across broad classes of drug receptors.

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