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Interaction of cyclic peptides and depsipeptides with calmodulin
K A Mereish1, R Solow, D L Bunner
1Medical Division Research Laboratory, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
Peptide Research
|September 1, 1990
Summary
Several cyclic peptides, including cyclosporin A and gramicidin-S, bind calmodulin (CaM) and inhibit CaM-dependent enzymes like phosphodiesterase (PDE). This interaction may alter cellular signaling pathways.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Calmodulin (CaM) is a crucial calcium-binding protein regulating numerous cellular processes.
- CaM-dependent enzymes play vital roles in signal transduction pathways.
- Small peptides are known to modulate CaM activity and enzyme function.
Purpose of the Study:
- To investigate the binding of various cyclic peptides to calmodulin (CaM).
- To determine the inhibitory effects of these peptides on CaM-dependent phosphodiesterase (PDE) activity.
- To explore potential alterations in CaM conformation and function upon peptide binding.
Main Methods:
- Spectroscopic analysis (e.g., fluorescence) to detect CaM-peptide interactions.
- Enzyme inhibition assays to quantify PDE activity.
- Determination of binding constants (Kd) and half-maximal inhibitory concentrations (IC50).
Main Results:
- Cyclic peptides cyclosporin A (CSA), gramicidin-S (GRS), microcystin-LR (MLR), valinomycin (VLM), and enniatin-B (ENB) bind to CaM.
- These peptides inhibit CaM-dependent PDE activity in a dose-dependent manner.
- Distinct binding sites or conformational changes were suggested for different peptide classes based on spectral data.
Conclusions:
- The peptides MLR, VLM, and ENB bind to CaM and inhibit CaM-dependent PDE activity, representing a novel observation.
- Peptide binding to CaM can induce conformational changes, affecting CaM's ability to regulate downstream enzymes.
- This interaction highlights a potential mechanism for modulating signal transduction pathways involving CaM.