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Related Concept Videos

GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
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GPCR Desensitization01:12

GPCR Desensitization

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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...
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Allosteric Regulation01:08

Allosteric Regulation

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Allosteric regulation of enzymes occurs when the binding of an effector molecule to a site that is different from the active site causes a change in the enzymatic activity. This alternate site is called an allosteric site, and an enzyme can contain more than one of these sites. Allosteric regulation can either be positive or negative, resulting in an increase or decrease in enzyme activity. Most enzymes that display allosteric regulation are metabolic enzymes involved in the degradation or...
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Allosteric Proteins-ATCase01:19

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Binding sites linkages can regulate a protein's function.  For example, enzyme activity is often regulated through a feedback mechanism where the end product of the biochemical process serves as an inhibitor.
Aspartate transcarbamoylase (ATCase) is a cytosolic enzyme that catalyzes the condensation of L-aspartate and carbamoyl phosphate to  N-carbamoyl-L-aspartate. This reaction is the first step in pyrimidine biosynthesis. UTP and CTP, the end products of the pyrimidine synthesis...
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G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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G Protein-Coupled Receptors or GPCRs are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to sensory stimuli such as light, odors, hormones, cytokines, or neurotransmitters.
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Transducer Mechanism: G Protein–Coupled Receptors01:30

Transducer Mechanism: G Protein–Coupled Receptors

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G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
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Related Experiment Video

Updated: Jan 4, 2026

A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators

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GPCR Allosteric Modulator Discovery.

Yiran Wu1, Jiahui Tong1,2, Kang Ding1

  • 1iHuman Institute, ShanghaiTech University, Shanghai, China.

Advances in Experimental Medicine and Biology
|November 11, 2019
PubMed
Summary

G protein-coupled receptors (GPCRs) are crucial drug targets. Allosteric ligands offer advantages, and understanding their mechanisms via structural biology is key to developing new therapeutics.

Keywords:
GPCRallosteric modulatordrug discoverymembrane protein structures

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Area of Science:

  • Pharmacology
  • Structural Biology
  • Drug Discovery

Background:

  • G protein-coupled receptors (GPCRs) are vital physiological regulators and a major drug target class.
  • Allosteric ligands for GPCRs offer potential advantages over orthosteric ligands, including improved selectivity and biased signaling.
  • The discovery and development of GPCR allosteric ligands are challenging, limiting their clinical translation.

Purpose of the Study:

  • To summarize GPCR allosteric modulating mechanisms.
  • To discuss validated allosteric mechanisms using GPCR-allosteric modulator complex structures.
  • To highlight the importance of structural biology in understanding GPCR allosteric ligand action.

Main Methods:

  • Review of existing literature on GPCR allosteric modulators.
  • Analysis of structural data from allosteric modulator-GPCR complexes.
  • Discussion of validated allosteric modulation mechanisms.

Main Results:

  • Identification and categorization of various GPCR allosteric modulating mechanisms.
  • Structural insights into how allosteric modulators interact with GPCRs.
  • Validation of specific allosteric mechanisms through complex structural analysis.

Conclusions:

  • Understanding GPCR allosteric mechanisms is critical for novel therapeutic discovery.
  • Structural biology advancements are crucial for elucidating allosteric sites and ligand interactions.
  • Further research into GPCR allosteric ligands can lead to improved drug development.