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Interaction of palytoxin with red cells: structure-function studies
M T Tosteson1, D R Scriven, A K Bharadwaj
1Laboratory for Membrane Transport, Harvard Medical School, Boston, MA 02115, USA.
Summary
Palytoxin (PTX) analogs showed reduced ability to increase red blood cell permeability and inhibit the Na+,K+-ATPase. Both ends of PTX are crucial for its interaction with the Na+,K+-pump receptor.
Area of Science:
- Marine natural products
- Biochemistry
- Cell membrane transport
Background:
- Palytoxin (PTX) is a potent marine toxin affecting red blood cell membranes.
- PTX inhibits the (Na+,K+)-activated ATPase, a key ion pump.
- PTX competes with ouabain for a binding site on the Na+,K+-pump.
Purpose of the Study:
- To synthesize and evaluate PTX analogs for covalent binding to identify the PTX binding site.
- To assess the impact of structural modifications on PTX's biological activity.
Main Methods:
- Synthesis of PTX analogs with modifications at one or both ends.
- Testing analog potency in increasing red blood cell cation permeability.
- Assessing inhibition of purified (Na+,K+-ATPase).
- Evaluating competition with ouabain for binding sites.
Main Results:
- PTX analogs significantly decreased cation permeability and Na+,K+-ATPase inhibition.
- Analog potency was 100-1000 times less than PTX in ouabain competition.
- Effects of PTX and its analogs were reversible by ouabain.
Conclusions:
- Both ends of the palytoxin molecule are essential for its interaction with the Na+,K+-pump.
- Structural modifications significantly alter PTX binding affinity and biological activity.
- PTX analogs are less effective than PTX in targeting the Na+,K+-pump.