The interaction of phomopsin A with bovine brain tubulin.
Phomopsin A is an anti-mitotic compound from the fungus Phomopsis leptostroniformis which is a potent inhibitor of microtubule assembly in vitro; like maytansine, it is known to compete with vinblastine for binding to tubulin (E. Lacey, J. A. Edgar, and C. C. J. Culvenor (1987) Biochem. Pharmacol. 36, 2133-2138). A major difference between the effects of maytansine and vinblastine is that vinblastine is a potent inhibitor of tubulin decay, whereas maytansine has little or no effect on decay. Since phomopsin A is structurally distinct from either maytansine or vinblastine, tubulin decay may be measured by either the time-dependent loss of the ability to bind to [3H]colchicine or the time-dependent increase in the binding of bis(8-anilinonaphthalene 1-sulfonate) (BisANS) to tubulin. By either method, phomopsin A was found to be a much stronger inhibitor of tubulin decay than is vinblastine or any other drug yet tested, and in fact, when decay is measured by the increase of BisANS binding, phomopsin A appears to stop the process entirely. This may prove to be useful in the determination of the higher-order structure of the tubulin molecule.
Ludueña
R F
RF
Department of Biochemistry, University of Texas Health Science Center, San Antonio 78284-7760.
Prasad
V
V
Roach
M C
MC
Lacey
E
E
D000817:Anilino Naphthalenesulfonates / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry; D002417:Cattle; D003078:Colchicine / Q000378:metabolism; D005456:Fluorescent Dyes; D007700:Kinetics; D008453:Maytansine / Q000494:pharmacology; D015394:Molecular Structure; D009183:Mycotoxins / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D014404:Tubulin / Q000378:metabolism*; D014747:Vinblastine / Q000494:pharmacology; D009842:Oligopeptides
D000817:Anilino Naphthalenesulfonates; D003078:Colchicine; D005456:Fluorescent Dyes; D008453:Maytansine; D009183:Mycotoxins; D014404:Tubulin; D014747:Vinblastine; C035763:5,5'-bis(8-(phenylamino)-1-naphthalenesulfonate); C035753:phomopsin; D009842:Oligopeptides