Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
Evolutionary Relationships through Genome Comparisons02:54

Evolutionary Relationships through Genome Comparisons

Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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 cells.
Two...
Conserved Binding Sites01:49

Conserved Binding Sites

Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
G Protein-coupled Receptors01:15

G Protein-coupled Receptors

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.
GPCRs are also called heptahelical, 7TM, or serpentine receptors, and consist of seven (H1-H7) transmembrane alpha-helices that span the bilayer to form a cylindrical core. The transmembrane helices are connected by three extracellular loops and three...
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence its...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Teaching bioinformatics with generative AI: judgment, uncertainty, and responsibility.

Journal of microbiology & biology education·2026
Same author

When Complex Models Fit the Wrong Mechanistic Complexity in Phylogenomic Analysis.

Journal of molecular evolution·2026
Same author

AI-assisted semi-automated segmentation for tooth volume analysis in postmortem CT imaging: evaluation of forensic applicability.

International journal of computerized dentistry·2026
Same author

How Binding Affinity and Binding Specificity Map to Sequence Space.

Journal of molecular evolution·2026
Same author

2025 Zuckerkandl Prize.

Journal of molecular evolution·2026
Same author

Perspectives on Orthology During the Quest for Orthologs.

Journal of molecular evolution·2025

Related Experiment Video

Updated: Jul 19, 2026

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

Using evolutionary information and ancestral sequences to understand the sequence-function relationship in GLP-1

Marie Skovgaard1, Janos T Kodra, Dorte Xenia Gram

  • 1Novo Nordisk A/S, Novo Nordisk Park, DK-2760 Måløv, Denmark. marie.skovgaard@gmail.com

Journal of Molecular Biology
|September 23, 2006
PubMed
Summary

Researchers explored glucagon-like peptide-1 (GLP-1) variants from different species to enhance therapeutic potential for type 2 diabetes. Evolutionary insights revealed specific peptide sequences with improved enzymatic stability, offering new avenues for drug development.

More Related Videos

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
05:08

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus
09:22

Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus

Published on: May 31, 2022

Related Experiment Videos

Last Updated: Jul 19, 2026

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
11:49

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

Published on: July 28, 2014

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins
05:08

Application of I TASSER, trRosetta, UCSF Chimera, HADDOCK server, and HEX loria for De Novo and In Silico Design of Proteins

Published on: July 8, 2025

Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus
09:22

Multi-Faceted Mass Spectrometric Investigation of Neuropeptides in Callinectes sapidus

Published on: May 31, 2022

Area of Science:

  • Biochemistry
  • Evolutionary Biology
  • Pharmacology

Background:

  • Glucagon-like peptide-1 (GLP-1) is a key incretin hormone with significant therapeutic promise for managing type 2 diabetes.
  • Diverse GLP-1 sequences exist across species, with some exhibiting the ability to bind and activate the human GLP-1 receptor.

Purpose of the Study:

  • To investigate the evolutionary history of GLP-1 and identify sequence variations that enhance enzymatic stability.
  • To engineer novel GLP-1 peptides with improved therapeutic properties for type 2 diabetes treatment.

Main Methods:

  • Testing of various amphibian GLP-1 sequences for binding and activation of the human GLP-1 receptor.
  • Analysis of in vitro potency and enzymatic stability of different GLP-1 peptides.
  • Application of ancestral sequence reconstruction and residue mapping on evolutionary branches for protein engineering.

Main Results:

  • While in vitro potency for the human GLP-1 receptor showed minimal variation, significant differences in enzymatic stability were observed among tested peptides.
  • Two peptides, phylogenetically related despite originating from Amphibia and Reptilia, demonstrated increased enzymatic stability.
  • Ancestral sequence reconstruction of frog GLP-1 precursors did not yield increased stability, though receptor activation was maintained.
  • Residue mapping identified peptides with sustained receptor potency and enhanced enzymatic stability.

Conclusions:

  • Evolutionary analysis and protein engineering can yield GLP-1 variants with improved stability for potential therapeutic applications in type 2 diabetes.
  • Specific evolutionary pathways have led to enhanced enzymatic stability in GLP-1 peptides, offering a novel strategy for protein engineering.
  • This study highlights a new approach to protein engineering by leveraging evolutionary data to design more stable and effective therapeutic peptides.