A Marine Natural Product Inhibitor of Kinesin Motors

Members of the kinesin superfamily of motor proteins are essential for mitotic and meiotic spindle organization, chromosome segregation, organelle and vesicle transport, and many other processes that require microtubule-based transport. A compound, adocia-sulfate-2, was isolated from a marine sponge...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1998-04, Vol.280 (5361), p.292-295
Main Authors: Sakowicz, Roman, Berdelis, Michael S., Ray, Krishanu, Blackburn, Christine L., Hopmann, Cordula, Faulkner, D. John, Lawrence S. B. Goldstein
Format: Article
Language:English
Subjects:
Adenosine Diphosphate - metabolism
Adenosine triphosphatases
Adenosine Triphosphatases - antagonists & inhibitors
Adenosine Triphosphate - metabolism
Amino acids
Analytical, structural and metabolic biochemistry
Animals
Binding Sites
Biological and medical sciences
Cell Division - drug effects
Chromatin
Chromosomes
Drosophila
Drosophila - embryology
Embryos
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - isolation & purification
Enzyme Inhibitors - pharmacology
Enzymes
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Haliclona
HeLa Cells
Humans
Hydrolases
Inhibition
Kinesin
Kinesin - antagonists & inhibitors
Kinesin - metabolism
Kinetics
Marine
Marine biology
Microtubules - metabolism
Mitosis - drug effects
Molecules
Observations
Porifera
Porifera - chemistry
Proteins
Sponges
Sulfuric Acid Esters - chemistry
Sulfuric Acid Esters - isolation & purification
Sulfuric Acid Esters - pharmacology
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Summary:Members of the kinesin superfamily of motor proteins are essential for mitotic and meiotic spindle organization, chromosome segregation, organelle and vesicle transport, and many other processes that require microtubule-based transport. A compound, adocia-sulfate-2, was isolated from a marine sponge, Haliclona (also known as Adocia) species, that inhibited kinesin activity by targeting its motor domain and mimicking the activity of the microtubule. Thus, the kinesin-microtubule interaction site could be a useful target for small molecule modulators, and adociasulfate-2 should serve as an archetype for specific inhibitors of kinesin functions.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.280.5361.292