Ustiloxins, new antimitotic cyclic peptides: interaction with porcine brain tubulin.
Biochemical and electron microscopic studies demonstrated that ustiloxins A-D, which are antimitotic 13-membered cyclic peptides produced by the rice plant pathogen Ustilaginoidea virens, strongly inhibited the polymerization of porcine brain tubulin in vitro and depolymerized pre-formed microtubules. The IC50 values of polymerization inhibited by ustiloxins A-D were determined to be 0.7, 2.8, 4.4 and 6.6 microM, respectively, under the experimental conditions used, indicating that ustiloxin A is the most potent inhibitor of tubulin polymerization currently known. Ustiloxins A-C were found to inhibit the binding of radiolabelled rhizoxin to tubulin with inhibition constants (Ki) of 0.08, 0.13 and 0.23 microM, respectively, and also inhibited the binding of radiolabelled phomopsin A as strongly as rhizoxin. These results suggest that the binding site of ustiloxins is identical with that of rhizoxin.
Li
Y
Y
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Koiso
Y
Y
Kobayashi
H
H
Hashimoto
Y
Y
Iwasaki
S
S
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001665:Binding Sites / Q000187:drug effects; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007783:Lactones / Q000378:metabolism; D018942:Macrolides; D008969:Molecular Sequence Data; D009183:Mycotoxins / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides; D010456:Peptides, Cyclic / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine; D014404:Tubulin / Q000737:chemistry / Q000378:metabolism*; D009842:Oligopeptides
D000900:Anti-Bacterial Agents; D007783:Lactones; D018942:Macrolides; D009183:Mycotoxins; D010455:Peptides; D010456:Peptides, Cyclic; D014404:Tubulin; C089077:ustiloxin B; C087237:ustiloxin A; C089079:ustiloxin D; C089078:ustiloxin C; C035753:phomopsin; D009842:Oligopeptides; C041443:rhizoxin