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, adociasulfate-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.
Sakowicz
R
R
Department of Pharmacology, Division of Cellular and Molecular Medicine, Howard Hughes Medical Institute, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0683, USA.
Berdelis
M S
MS
Ray
K
K
Blackburn
C L
CL
Hopmann
C
C
Faulkner
D J
DJ
Goldstein
L S
LS
D000244:Adenosine Diphosphate / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D004330:Drosophila / Q000196:embryology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008870:Microtubules / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D011161:Porifera / Q000737:chemistry*; D013463:Sulfuric Acid Esters / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013463:Sulfuric Acid Esters; C111568:adociasulfate-2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000251:Adenosine Triphosphatases; D016547:Kinesins