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Solution conformation of human big endothelin-1.
M L Donlan1, F K Brown, P W Jeffs
1Glaxo Research Institute, Research Triangle Park, NC 27709.
Journal of Biomolecular NMR
|September 1, 1992
Summary
Human big endothelin-1, a precursor to the vasoconstrictor endothelin-1, exhibits a defined core structure with a beta-turn and alpha-helix. The C-terminal region displays dynamic conformational flexibility.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biophysics
Background:
- Human big endothelin-1 is the precursor to endothelin-1, a potent vasoconstrictor.
- Understanding the conformation of big endothelin-1 is crucial for elucidating its biological function and processing.
Purpose of the Study:
- To determine the solution conformation of human big endothelin-1.
- To characterize the structural features of the peptide, including its core and C-terminal regions.
Main Methods:
- 1H NMR spectroscopy was employed to study the peptide.
- Nuclear Overhauser Effect (NOE) data were used as distance restraints.
- Distance geometry (DSPACE) and molecular mechanics/dynamics were used for structure refinement.
Main Results:
- A well-defined core region (residues 1-15) was identified, featuring a type II beta-turn (residues 5-8) and an alpha-helix (residues 9-16).
- The atomic root-mean-square difference for the core region backbone atoms was 1.56 Å.
- The C-terminal region (residues 17-34) did not adopt a single conformation but existed as a dynamic equilibrium of conformers.
Conclusions:
- The core structure of human big endothelin-1 is similar to that of endothelin-1.
- The C-terminal region of human big endothelin-1 is conformationally flexible under the studied conditions (pH 3.0, 20-30°C).
- These findings provide insights into the structural dynamics of big endothelin-1 and its potential role in endothelin-1 formation.