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 Experiment Videos

[Lys(-2)-Arg(-1)]endothelin-1 solution structure by two-dimensional 1H-NMR: possible involvement of electrostatic

A Aumelas1, L Chiche, S Kubo

  • 1Centre de Biochimie Structurale CNRS UMR C9955, INSERM U414, Faculté de Pharmacie, Montpellier, France.

Biochemistry
|April 11, 1995
PubMed
Summary

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

Extra-hepatic cholangiocarcinoma diagnosis: from classical pathological analysis to the emerging omics tests.

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology·2026
Same author

ASO Author's Reflections: Extrahepatic Cholangiocarcinoma as an Oncological Consistent Entity: Insights from Proteomic Profiling and Lack of Anatomical Impact.

Annals of surgical oncology·2025
Same author

Blurring the Anatomical Lines in Extrahepatic Cholangiocarcinoma: An Integrated Clinic-Oncological and Exploratory Proteomic Comparison of Perihilar and Distal Tumors.

Annals of surgical oncology·2025
Same author

[Between the normal and the pathological: The concept of pre-disease applied to systemic autoimmune rheumatic diseases].

La Revue de medecine interne·2024
Same author

Outcome and prognosis of isolated carotid vasculitis.

Journal of autoimmunity·2024
Same author

[Managing cancer immunotherapy toxicities: Challenges and rechallenges for (young) internists].

La Revue de medecine interne·2023

Adding a dipeptide to endothelin-1 (ET-1) improves disulfide bonds and reduces activity. This study reveals how electrostatic interactions, like the Arg(-1)-Glu10 salt bridge, stabilize the peptide structure and influence its biological function.

Area of Science:

  • Biochemistry
  • Structural Biology
  • Molecular Biophysics

Background:

  • Endothelin-1 (ET-1) is a potent vasoconstrictor.
  • The precursor protein contains a Lys(-2)-Arg(-1) dipeptide.
  • KR-ET-1, a modified ET-1, shows improved disulfide bond formation and reduced activity.

Purpose of the Study:

  • To investigate the three-dimensional structure of KR-ET-1.
  • To elucidate the role of electrostatic interactions in KR-ET-1 conformation and function.
  • To understand the structural basis for improved disulfide bond formation and decreased biological activity.

Main Methods:

  • Circular Dichroism (CD) spectroscopy.
  • Nuclear Magnetic Resonance (NMR) spectroscopy (2D NMR).
  • Distance geometry calculations, simulated annealing, and molecular dynamics.

Related Experiment Videos

Main Results:

  • KR-ET-1 adopts different conformations in carboxylic acid and carboxylate states.
  • The carboxylate state shows an extended helix and stabilized C-terminus, involving an Arg(-1)-Glu10 salt bridge.
  • Hydrophobic interactions and an electrostatic network further stabilize the structure.
  • Reduced mobility of Trp21 in KR-ET-1 correlates with decreased biological activity.

Conclusions:

  • The Arg(-1)-Glu10 salt bridge is crucial for improved disulfide bond formation in KR-ET-1.
  • These electrostatic interactions may be vital for native folding of the ET-1 precursor protein.
  • Structural modifications, particularly Trp21 environment, explain the reduced biological activity of KR-ET-1.