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Linearization of a naturally occurring circular protein maintains structure but eliminates hemolytic activity.
- Source :
-
Biochemistry [Biochemistry] 2003 Jun 10; Vol. 42 (22), pp. 6688-95. - Publication Year :
- 2003
-
Abstract
- Cyclotides are a recently discovered family of disulfide rich proteins from plants that contain a circular protein backbone. They are exceptionally stable, as exemplified by their use in native medicine of the prototypic cyclotide kalata B1. The peptide retains uterotonic activity after the plant from which it is derived is boiled to make a medicinal tea. The circular backbone is thought to be in part responsible for the stability of the cyclotides, and to investigate its role in determining structure and biological activity, an acyclic derivative, des-(24-28)-kalata B1, was chemically synthesized and purified. This derivative has five residues removed from the 29-amino acid circular backbone of kalata B1 in a loop region corresponding to a processing site in the biosynthetic precursor protein. Two-dimensional NMR spectra of the peptide were recorded, assigned, and used to identify a series of distance, angle, and hydrogen bonding restraints. These were in turn used to determine a representative family of solution structures. Of particular interest was a determination of the structural similarities and differences between des-(24-28)-kalata B1 and native kalata B1. Although the overall three-dimensional fold remains very similar to that of the native circular protein, removal of residues 24-28 of kalata B1 causes disruption of some structural features that are important to the overall stability. Furthermore, loss of hemolytic activity is associated with backbone truncation and linearization.
- Subjects :
- Amino Acid Sequence
Conserved Sequence
Cyclization
Dose-Response Relationship, Drug
Melitten pharmacology
Models, Molecular
Molecular Sequence Data
Nuclear Magnetic Resonance, Biomolecular
Peptides, Cyclic genetics
Protein Structure, Secondary
Cyclotides
Hemolysis drug effects
Peptides, Cyclic chemistry
Peptides, Cyclic pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2960
- Volume :
- 42
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Biochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 12779323
- Full Text :
- https://doi.org/10.1021/bi027323n